Round ligament management during minimally invasive groin hernia repair in women: a systematic review and meta-analysis.

BACKGROUND: Female sex has been associated with worse outcomes after groin hernia repair (GHR), including a higher rate of chronic pain and recurrence. Most of the studies in GHR are performed in males, and the recommendations for females extrapolate from these studies, even though females have anatomy intricacies. The round ligament of the uterus (RLU) is associated with pelvic stabilization and plays a role in sensory function. Transection of the RLU during GHR is controversial as it can allow easier mesh placement but can favor genitourinary complications and chronic pain. As no previous meta-analysis compared preserving versus transecting the RLU during minimally invasive (MIS) GHR, we aim to perform a systematic review and meta-analysis evaluating surgical outcomes comparing the approaches. METHODS: Cochrane Central, Embase, and PubMed databases were systematically searched for studies comparing transection versus preservation of the RLU in MIS groin hernia surgeries. Outcomes assessed were operative time, bleeding, surgical site events, hospital stay, chronic pain, paresthesia, recurrence rates, and genital prolapse rates. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics. A review protocol for this meta-analysis was registered at PROSPERO (CRD 42023467146). RESULTS: 1738 studies were screened. A total of six studies, comprising 1131 women, were included, of whom 652 (57.6%) had preservation of the RLU during MIS groin hernia repair. We found no statistical difference regarding chronic pain, paresthesia, recurrence rates, and postoperative complications. We found a longer operative time for the preservation group (MD 6.84 min; 95% CI 3.0-10.68; P = 0.0005; I2 = 74%). CONCLUSION: Transecting the RLU reduces the operative time during MIS GHR with no difference regarding postoperative complication rates. Although transection appears safe, further prospective randomized studies with long-term follow-up and patient-reported outcomes are necessary to define the optimal management of RLU during MIS GHR.

Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.

BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. PATIENTS AND METHODS: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. RESULTS: BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by in vitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1, RIF1 or PAXIP1] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. CONCLUSIONS: These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.

Transinguinal preperitoneal (TIPP) versus Lichtenstein for inguinal hernia repair: a systematic review and meta-analysis.

PURPOSE: We aimed to perform a systematic review and meta-analysis comparing postoperative outcomes in inguinal hernia repair with TIPP versus Lichtenstein technique. METHODS: Cochrane Central, Scopus, and PubMed were systematically searched for studies comparing TIPP and Lichtenstein´s technique for inguinal hernia repair. Outcomes assessed were operative time, bleeding, surgical site events, hospital stay, the Visual Analogue Pain Score, chronic pain, paresthesia rates, and recurrence. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics and random-risk effect was used if I2 > 25%. RESULTS: 790 studies were screened and 44 were thoroughly reviewed. A total of nine studies, comprising 8428 patients were included, of whom 4185 (49.7%) received TIPP and 4243 (50.3%) received Lichtenstein. We found that TIPP presented less chronic pain (OR 0.43; 95% CI 0.20-0.93 P = 0.03; I2 = 84%) and paresthesia rates (OR 0.27; 95% CI 0.07-0.99; P = 0.05; I2 = 63%) than Lichtenstein group. In addition, TIPP was associated with a lower VAS pain score at 14 postoperative day (MD - 0.93; 95% CI - 1.48 to - 0.39; P = 0.0007; I2 = 99%). The data showed a lower operative time with the TIPP technique (MD - 7.18; 95% CI - 12.50, - 1.87; P = 0.008; I2 = 94%). We found no statistical difference between groups regarding the other outcomes analyzed. CONCLUSION: TIPP may be a valuable technique for inguinal hernias. It was associated with lower chronic pain, and paresthesia when compared to Lichtenstein technique. Further long-term randomized studies are necessary to confirm our findings. Study registration A review protocol for this meta-analysis was registered at PROSPERO (CRD42023434909).

Mesh repair versus non-mesh repair for incarcerated and strangulated groin hernia: an updated systematic review and meta-analysis.

BACKGROUND: Mesh repair in incarcerated or strangulated groin hernia is controversial, especially when bowel resection is required. We aimed to perform a meta-analysis comparing mesh and non-mesh repair in patients undergoing emergency groin hernia repair. METHODS: We performed a literature search of databases to identify studies comparing mesh and primary suture repair of patients with incarcerated or strangulated inguinal or femoral hernias who underwent emergency surgery. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics. RESULTS: 1095 studies were screened and 101 were thoroughly reviewed. Twenty observational studies and four randomized controlled trials comprising 12,402 patients were included. We found that mesh-based repair had reduced recurrence (OR 0.36; 95% CI 0.19, 0.67; P = 0.001; I2 = 35%), length of hospital stay (OR - 1.02; 95% CI - 1.87, - 0.17; P = 0.02; I2 = 94%) and operative time (OR - 9.21; 95% CI - 16.82, - 1.61; P = 0.02; I2 = 95%) without increasing surgical site infection, mortality or postoperative complications such as seroma, chronic, ileus or urinary retention. In the subgroup analysis of patients that underwent bowel resection, we found that mesh repair was associated with an increased risk of surgical site infection (OR 1.74; 95% CI 1.04, 2.91; P = 0.04; I2 = 9%). CONCLUSIONS: Mesh repair for incarcerated and strangulated groin hernias reduces recurrence without an increase in postoperative complications and should be considered in clean cases. However, in the setting of bowel resection, mesh repair might increase the incidence of surgical site infection.

Management and outcomes of obturator hernias: a systematic review and meta-analysis.

PURPOSE: Obturator Hernia (OH) is a rare type of abdominal wall hernia. It usually occurs in elderly women with late symptomatic presentation, increasing mortality rates. Surgery is the standard of care for OH, and laparotomy with simple suture closure of the defect is commonly used. Given the rarity of this disease, large studies are lacking, and data to drive management are still limited. This systematic review and meta-analysis aimed to describe current surgical options for OHs, with a focus on comparing the effectiveness and safety of mesh use with primary repair. METHODS: PubMed, EMBASE, and Cochrane were searched for studies comparing mesh and non-mesh repair for OH. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. RESULTS: One thousand seven hundred and sixty studies were screened and sixty-seven were thoroughly reviewed. We included 13 observational studies with 351 patients surgically treated for OH with mesh or non-mesh repair. One hundred and twenty (34.2%) patients underwent mesh repair and two hundred and thirty-one (65.81%) underwent non-mesh repair. A total of 145 (41.3%) underwent bowel resection, with the majority having a non-mesh repair performed. Hernia recurrence was significantly higher in patients who underwent hernia repair without mesh (RR 0.31; 95% CI 0.11-0.94; p = 0.04). There were no differences in mortality (RR 0.64; 95% CI 0.25-1.62; p = 0.34; I2 = 0%) or complication rates (RR 0.59; 95% CI 0.28-1.25; p = 0.17; I2 = 50%) between both groups. CONCLUSION: Mesh repair in OH was associated with lower recurrence rates without an increase in postoperative complications. While mesh in clean cases is more likely to offer benefits, an overall recommendation regarding its use in OH repair cannot be made due to potential bias across studies. Given that many OH patients are frail and present emergently, the decision to use mesh is complex and should consider the patient's clinical status, comorbidities, and degree of intraoperative contamination.

[The clinical value of serum GPC3 level in predicting recurrence of patients with primary hepatocellular carcinoma].

Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ2=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ2=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ2=4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ2=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.

A computational model for the transit of a cancer cell through a constricted microchannel.

We propose a three-dimensional computational model to simulate the transient deformation of suspended cancer cells flowing through a constricted microchannel. We model the cell as a liquid droplet enclosed by a viscoelastic membrane, and its nucleus as a smaller stiffer capsule. The cell deformation and its interaction with the suspending fluid are solved through a well-tested immersed boundary lattice Boltzmann method. To identify a minimal mechanical model that can quantitatively predict the transient cell deformation in a constricted channel, we conduct extensive parametric studies of the effects of the rheology of the cell membrane, cytoplasm and nucleus and compare the results with a recent experiment conducted on human leukaemia cells. We find that excellent agreement with the experiment can be achieved by employing a viscoelastic cell membrane model with the membrane viscosity depending on its mode of deformation (shear versus elongation). The cell nucleus limits the overall deformation of the whole cell, and its effect increases with the nucleus size. The present computational model may be used to guide the design of microfluidic devices to sort cancer cells, or to inversely infer cell mechanical properties from their flow-induced deformation.

Management of diastasis recti during ventral hernia repair: an analysis of the abdominal core health quality collaborative.

PURPOSE: Advancements of minimally invasive techniques leveraged routine repair of concomitant diastasis recti (DR), as those approaches facilitate fascial plication and wide mesh overlap while obviating skin incision and/or undermining. Nevertheless, evidence on the value of such intervention is lacking. We aimed to investigate the management and outcomes of concomitant DR during ventral hernia repair (VHR + DR) from surgeons participating in the Abdominal Core Health Quality Collaborative (ACHQC). METHODS: Patients who have undergone VHR + DR with a minimum 30-day follow-up complete were identified. Outcomes of interest included operative details, surgical site occurrences (SSO), medical complications, and readmissions. RESULTS: 169 patients (51% female, median age 46, median body mass index 31 kg/m2) were identified. Most hernias were primary (64% umbilical, 28% epigastric). Median hernia width was 3 cm (IQR 2-4) and median diastasis width and length were 4 cm (IQR 3-6) and 15 cm (IQR 10-20), respectively. Most operations were robotic (79%), with a synthetic mesh (92%) placed as a sublay (72%; 59% retromuscular, 13% preperitoneal). DR was repaired with absorbable (92%) and running suture (93%). Considering our cohort's relatively small diastasis and hernia size, a high rate of transversus abdominis release was noted (14.7%). 76% were discharged the same day and the 30-day readmission rate was 2% (2 ileus, 1 pneumonia). SSO rate was 4% (6 seromas, 1 skin necrosis) and only one patient required a procedural intervention. CONCLUSIONS: ACHQC participating surgeons usually perform VHR + DR robotically with a retromuscular synthetic mesh and close the DR with running absorbable sutures. Short-term complications occurred in approximately 6% of patients and were mainly managed without interventions. Larger studies with longer-term follow-up are needed to determine the value of VHR + DR.

[Efficacy and safety of combination therapy with chemotherapy, programmed death-1 inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma].

Objective: To investigate the efficacy and safety of the combination therapy with chemotherapy, programmed death-1 (PD-1) inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma (DDLPS). Methods: The clinical data of patients with dedifferentiated liposarcoma who received chemotherapy combined with PD-1 inhibitor and anlotinib in the Department of Medical Oncology, Zhongshan Hospital Affiliated to Fudan University from January 1, 2020 to November 30, 2021 were retrospectively analyzed. A total of 24 patients were included in this study, including 12 males and 12 females, with a median age of onset of 56 years (range, 31-69 years). Efficacy and safety in those patients were assessed. Results: All patients had unresectable or metastatic dedifferentiated liposarcoma with G2 (moderate differentiation) or G3 (differential differentiation) in a concise three-grade grading scheme of tumor pathology. Twelve patients received the regimen as the first-line treatment, while the other 7 taken the regimen as second-line treatment and 5 as third-line or above. The median follow-up time for overall survival (OS) was 7.7 months. The overall response rate (ORR) was 20.8% (5/24) and disease control rate (DCR) was 83.3% (20/24) with 5 partial response (PR), 15 stable disease (SD) and 4 progressive disease (PD). Overall, the median progression-free survival (PFS) was 4.9 months (95%CI: 3.4-16.2 months). The ORR of anthracycline-based, eribulin-based or gemcitabine-based regimens was 1/12, 2/6 and 2/6, respectively; and the median PFS was 7.7, 7.3 and 4.4 months, respectively. Waterfall plots showed notable tumor shrinkage of any degree in eribulin and gemcitabine-based regimens(3/6 and 2/6, respectively), while there were more patients presented with SD in anthracycline-based group(9/12). Common adverse reactions included myelosuppression, fatigue, anorexia, rash, pruritus, palpitate, hypothyroidism and hypertension. Conclusions: The combination regimen with chemotherapy, PD-1 inhibitor and anlotinib in the treatment of advanced DDLPS is effective and well tolerable. There are more responders in eribulin or gemcitabine-based regimens.

[Efficacy analysis of selective genicular artery embolization in the treatment of knee pain secondary to osteoarthritis].

Objective: To evaluate the efficacy and safety of selective genicular artery embolization for the treatment of the knee pain secondary to osteoarthritis. Methods: From October 2020 to July 2021, 17 patients (23 knees) aged (68±7) years with moderate to severe knee pain secondary to knee osteoarthritis were prospectively included in the General Hospital of Ningxia Medical University. There were 6 males and 11 females included in this research. Patients were assessed with knee pain, stiffness, and function with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, using the Kellgren-Lawrence (K-L) grading to evaluate the severity of KOA, and using the Magnetic Resonance Knee Osteoarthritis Score (MOAKS) to evaluate the MR imaging characteristics of the affected knee. Selective genicular artery embolization (GAE) was performed in all patients. The patients were followed up for 6 months after the procedure. Patients were assessed with the VAS score and WOMAC scale at 1 d, 1 week and 1, 3 and 6 months after the procedure to evaluate the clinical outcomes, including the improvement of knee joint pain, stiffness and function, as well as the occurrence of adverse reactions. Results: Three to seven genicular artery branches were superselected and embolized in 23 knees, and 4 to 7 genicular artery branches were embolized in 7 patients with K-L grade 4. The clinical improvement was 95.6% (22/23) at 1 month, 86.9% (20/23) at 3 months, and 91.3% (21/23) at 6 months. Twenty-three knees completed the 6-month follow-up, and the VAS score, WOMAC pain score, and total WOMAC score at 1, 3, and 6 months after surgery were (2.5±1.3), (3.4±2.4), and (19.7±9.8) points, (3.0±1.8), (4.5±3.4), and (22.3±11.3) points, (2.8±1.5), (4.1±3.0), and (20.5±11.0) points, which were lower than the (6.6±0.9), (11.4±2.6) and (47.0±12.0) points at baseline (all P<0.001). During the follow-up period, 7 patients had adverse reactions: 3 cases had skin ecchymosis in the femoral artery puncture area, 4 cases had knee joint stiffness and pain within 1 day after operation, which were relieved spontaneously in 1 week, 6 patients had joint clicking during extension and flexion activities after operation, of which 3 cases subsided spontaneously within 3 months after operation. None of the patients had major procedure-related adverse events. Conclusion: GAE has a high clinical improvement rate and a low incidence of adverse reactions in the treatment of the pain secondary to knee osteoarthritis, which provides a new treatment option for patients who fail to respond to conservative treatment.

Clinical outcomes of keratinized mucosa augmentation in jaws reconstructed with fibula or iliac bone flaps.

This prospective study was undertaken to evaluate the treatment outcomes of keratinized mucosa augmentation (KMA) on the buccal and palatal/lingual sides of implants in jaws reconstructed after oncological surgery. Forty-two implants in 12 patients whose jaws had been reconstructed with a fibula or iliac bone flap were included. KMA was performed at 3 months after implant placement; this included an apically displaced partial-thickness flap and a free gingival graft (FGG) around the implants to increase the keratinized mucosa width (KMW). Patients were followed up for at least 6 months post-surgery. KMW, shrinkage, and patient pain and discomfort measured on a visual analogue scale were analysed. A histological analysis was performed of tissue epithelium from two patients. The results showed that KMW was >2 mm on both the buccal and palatal/lingual sides during follow-up. Before surgery, histological analysis showed epithelium with no epithelial spikes; normal keratinized epithelial spikes were observed at 8 weeks after KMA. Greater KMW was observed around implants in reconstructed maxillae than around those in reconstructed mandibles (P < 0.001). Patients felt more pain at the donor site than at the recipient site during the first 3 days post-surgery. KMA with FGG was predictable in reconstructed jaws and may help maintain the long-term stability of implants.

[Application of serum markers in medullary thyroid carcinoma].

Objective: To discuss the diagnostic value of calcitonin(CT), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pro-gastrin releasing peptide (Pro-GRP) and chromogranin A (CgA) in the identification of medullary thyroid carcinoma (MTC). Methods: The CT levels in 105 cases of MTC, 50 cases of papillary thyroid carcinoma, 10 cases of thyroid follicular carcinoma, 5 cases of undifferentiated thyroid carcinoma, 50 cases of benign thyroid diseases, 30 cases of non-thyroid malignant tumors and 50 cases of healthy controls were measured from February 2017 to August 2019 at the Department of Clinical Laboratory, Cancer Hospital affliated to Fudan University. Additionally, 79 cases of MTC, 30 cases of non-MTC thyroid malignant tumors and 30 healthy controls were selected for the measurement of CEA, NSE, Pro-GRP and CgA levels. The receiver operating curve was utilized to clarify the area under the curve (AUC), sensitivity, and specificity of each indicator to distinguish between different groups. Results: The medians of CT concentrations in the group of MTC patients was 607.2 (152.5,2 777.5)pg/ml, which was statistically significantly higher than that of the subjects in the group of papillary thyroid carcinoma 1.48 (0.5,2.91)pg/ml, follicular thyroid carcinoma 1.90 (0.82,2.99)pg/ml, undifferentiated thyroid carcinoma 0.50 (0.50,4.93)pg/ml, benign thyroid disease 1.30 (0.50,2.79)pg/ml, non-thyroid malignancies 1.36 (0.50,2.89)pg/ml and healthy controls 2.05 (0.89,3.18)pg/ml. The sensitivity, specificity and AUC of CT to distinguish MTC vs. non-MTC patients was 96.2%, 99.3% and 0.99, respectively. The maximum diameter (>1 cm, P=0.001, OR=15.74) and number (>1, P=0.04, OR=3.4) of nodules were two independent risk factors for elevated CT. CEA (AUC=0.94), NSE (AUC=0.65), Pro-GRP (AUC=0.94) and CgA (AUC=0.83) could all distinguish MTC vs. non-MTC thyroid malignancies. The AUC, sensitivity and specificity by combining CT, CEA, NSE, Pro-GRP and CgA to differentiate MTC vs. non-MTC thyroid malignancies was 1, 100% and 100%, respectively. Conclusions: CT, CEA, NSE, Pro-GRP and CgA may be helpful for the auxiliary diagnosis of MTC. The combination of these indicators in the diagnosis of MTC has high sensitivity and specificity.

Evaluation of non-endemic pemphigus foliaceus in a large series of patients: a single-center retrospective study from Turkey focuses on the relapses

Abstract Background: Pemphigus foliaceus is exceedingly rare around the world, except within the few regions where it occurs as an endemic variant. Various factors can trigger immune mechanisms that induce pemphigus foliaceus or worsen its course. Objective: To determine the demographic and clinical characteristics of the patients with pemphigus foliaceus in a large series from a non-endemic country, investigate the triggering factors, and seasonal patterns. Methods: The data of the patients diagnosed with pemphigus foliaceus in the study's center between 1989-2018 were retrospectively analyzed. Results: Sixty-eight patients (mean age, 45.7 ± 14.5 years) were included in the study. The number of onsets reached its peak in spring-summer (p = 0.008). A total of 117 relapses occurred in 42 patients and were most common in spring-summer (not significant). Specific trigger factors were detected in 45 relapses. In the other 72 relapses, the peak was observed in spring-summer (p = 0.005). There were no significant differences in the demographic and clinical variables investigated between relapsed and non-relapsed patients. Study limitations: Retrospective design. Conclusions: Triggering factors could not be identified in more than half of the relapses in the study's series. The subgroup of relapses (without identified causes), as well as the onsets of the disease, showed a significant seasonal variation with a peak in spring-summer; however, the seasonal variable did not justify the total group of relapses. Although the seasonal variation may be caused by a combination of factors, UV radiation should be considered a trigger factor for the peaks in spring-summer, particularly in Turkey.

[Evaluation of intravascular therapy for cerebral ischemic tandem stenosis].

Objective: To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis. Methods: Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores. Results: Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients'mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2. Conclusion: Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.

[Clinical research progress in the treatment of intrabony defect by minimally invasive periodontal surgery].

Minimally invasive surgery develops rapidly in the periodontal treatments, especially in the periodontal regenerative treatment, in recent years. It supplements, to a certain extent, the insufficiency of the conventional periodontal regenerative treatment. The minimally invasive surgery has many advantages such as enhancing the healing process, reducing surgical chair time and minimizing patient discomfort, etc. It has been proved to improve the clinical effect and provide additional benefits compared to conventional approaches. At present, there are many studies on minimally invasive techniques used in tooth extraction or implant placement in China, but there are few reports on the application of periodontal minimally invasive surgical techniques. Thus based on the reviews of the literatures, this article describes the applications, advantages, indications, microsurgical instruments of minimally invasive periodontal surgery on the treatment of intrabony defect, including various minimally invasive surgical procedures. The review also demonstrates the therapeutic effects and research progress of minimally invasive periodontal surgery combined with biomaterials used in the treatments of intrabony defect. The present article may also provide reference for clinicians applying minimally invasive surgeries to treat intrabony defects.

[The value of serum glypican-3 level in aided diagnosis of patients with primary hepatocellular carcinoma].

Objective: To investigate the clinical value of glypican-3 (GPC3) detection in the diagnosis and therapy-monitoring of primary hepatocellular carcinoma (HCC). Methods: From March 2018 to May 2019, the patients with HCC were enrolled as the experimental group(n=166)from Fudan University Shanghai Cancer Centre, while the specimens from health control group(n=94) and benign control group (n=50) were analyzed. The serum of GPC3 and alpha fetoprotein (AFP)levels were respectively detected by ELISA and chemiluminescence. GPC3 detections combined with AFP etc. in accuracy of HCC diagnosis were explored by using Logistic regression analysis. Results: The serum GPC3 level in patients with HCC ［0.210 (0.048, 0.801)mg/L］ ［Median (quartile Q1, Q3)］ was significantly higher than those in healthy controls ［0.029(0.019, 0.052)mg/L］ and benign controls ［0.033(0.021, 0.043) mg/L］ (Z=-7.69, P<0.001).The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AFP were significantly different among the three groups (Z=-7.02, -6.85, -8.36 respectively, P<0.001). Among the serological indicators, it was related to ALT and AST (Z=-3.77, -4.09 respectively, P<0.001).The Cut-off level of GPC3 was determined as 0.077 mg/L by ROC curve. The sensitivity of the combined detection of serum GPC3 with AFP for HCC was up to 87.82%, the specificity was 77.86%, the negative predictive value was 84.29%, and the positive predictive value was 82.53%.The HCC-GPC3 model was constructed by using Logistic regression analysis. The area under the ROC curve was 0.882, the total sensitivity was 91.10%, and the total specificity was 72.73%. Further analysis showed that the serum GPC3 of patients with HCC was significantly lower ［0.454(0.019, 0.286) mg/L］ than that before surgery［0.608(0.039, 0.554）mg/L］(Z=-7.32, P<0.001). Conclusion: The detection of serum GPC3 can be applied to aid diagnosis and therapy-monitoring of HCC.The combination of GPC3 and AFP can improve the diagnostic efficiency of HCC.

[The etiological analysis of 260 hospitalized cases with bilateral adrenal lesions].

Objective: To summarize the etiologies of bilateral adrenal lesions and the changes of the disease profile in hospitalized patients. Methods: Bilateral adrenal lesion screening was conducted in all patients admitted to Peking University Third Hospital from 1994 to 2017. The etiologies and disease profiles of bilateral adrenal lesions were retrospectively analyzed. Results: A total of 260 patients with bilateral adrenal lesions were included in the study. There were 146 males and 114 females with a mean age of (55.4±16.2) years. The most common adrenal lesion was bilateral adrenal hyperplasia (75 cases, 28.8%), followed by bilateral adrenal adenomas (71 cases, 27.3%), metastatic carcinoma (51 cases, 19.6%), discordant bilateral adrenal lesions (27 cases, 10.4%), bilateral pheochromocytomas (13 cases, 5.0%), and others. The clear data of endocrine function evaluation could be found in 184 patients. Among them, 111 cases (60.3%) were nonfunctioning lessions, 34 cases (18.5%) with primary aldosteronism, 15 cases (8.1%) with pheochromocytoma, 13 cases (7.1%) with congenital adrenal hyperplasia, 6 cases (3.3%) with primary hypoadrenocorticism, and 5 cases (2.7%) with Cushing syndrome. Using every 8 years as a period of time, the number of hospitalized patients with bilateral adrenal lesions increased with years in three periods (8, 41 and 211 cases, respectively). Conclusions: The most common cause of bilateral adrenal lesions is adrenal hyperplasia in the hospitalized patients. More than half of bilateral adrenal lesions are nonfunctioning. In functional bilateral lesions, primary aldosteronism and pheochromocytoma account for a large proportion.

Efficacy of Oral Encochleated Amphotericin B in a Mouse Model of Cryptococcal Meningoencephalitis.

Cryptococcus neoformans is an encapsulated yeast responsible for approximately a quarter of a million deaths worldwide annually despite therapy, and upwards of 11% of HIV/AIDS-related deaths, rivaling the impact of tuberculosis and malaria. However, the most effective antifungal agent, amphotericin B, requires intravenous delivery and has significant renal and hematopoietic toxicity, making it difficult to utilize, especially in resource-limited settings. The present studies describe a new nanoparticle crystal encapsulated formulation of amphotericin B known as encochleated amphotericin B (CAmB) that seeks to provide an oral formulation that is low in toxicity and cost. Using a 3-day delayed model of murine cryptococcal meningoencephalitis and a large inoculum of a highly virulent strain of serotype A C. neoformans, CAmB, in combination with flucytosine, was found to have efficacy equivalent to parental amphotericin B deoxycholate with flucytosine and superior to oral fluconazole without untoward toxicity. Transport of fluorescent CAmB particles to brain as well as significant brain levels of amphotericin drug was demonstrated in treated mice, and immunological profiles were similar to those of mice treated with conventional amphotericin B. Additional toxicity studies using a standardized rat model showed negligible toxicity after a 28-day treatment schedule. These studies thus offer the potential for an efficacious oral formulation of a known fungicidal drug against intrathecal cryptococcal disease.IMPORTANCECryptococcus neoformans is a significant global fungal pathogen that kills an estimated quarter of a million HIV-infected individuals yearly and has poor outcomes despite therapy. The most effective therapy, amphotericin B, is highly effective in killing the fungus but is available only in highly toxic, intravenous formulations that are unavailable in most of the developing world, where cryptococcal disease in most prevalent. For example, in Ethiopia, reliance on the orally available antifungal fluconazole results in high mortality, even when initiated as preemptive therapy at the time of HIV diagnosis. Thus, alternative agents could result in significant saving of lives. Toward this end, the present work describes the development of a new formulation of amphotericin B (CAmB) that encapsulates the drug as a crystal lipid nanoparticle that facilitates oral absorption and prevents toxicity. Successful oral absorption of the drug was demonstrated in a mouse model that, in combination with the antifungal flucytosine, provided efficacy equal to a parental preparation of amphotericin B plus flucytosine. These studies demonstrate the potential for CAmB in combination with flucytosine to provide an effective oral formulation of a well-known, potent fungicidal drug combination.

Screening for syphilis with dual algorithms: analysis of discordant and concordant serology results in a population with a low prevalence of syphilis.

BACKGROUND: Currently, many laboratories have switched the traditional screening algorithm (TSA) to reverse screening algorithm (RSA) for the efficiencies in high-volume syphilis screening. However, confusions have been arisen regarding this paradigm shift. OBJECTIVE: To compare the performance of two algorithms with head-to-head mode. METHODS: Sera screening for syphilis were tested in parallel with chemiluminescence immunoassay (CIA) and toluidine red unheated serum test (TRUST). CIA-reactive sera from the RSA were reflexively tested with TRUST and confirmed with Treponema pallidum particle agglutination assay (TPPA), while the TRUST-reactive serology from the TSA were afterwards tested with TPPA. RESULTS: A total of 110 663 serum samples were screened. The RSA identified 2259 (2.0%) CIA-reactive results, of which 377 (16.7%) showed TPPA nonreactive results, while the TSA identified 934 (0.8%) TRUST-reactive results, of which 67 (7.2%) showed TPPA-nonreactive results. Among the 2259 CIA-reactive results, 1392 (61.6%) were TRUST-nonreactive, of which 350 (25.1%) were TPPA-nonreactive. A total of 182 sera from the 350 TPPA-nonreactive sera were further tested by a second CIA (VITROS Syphilis TPA, VITROS TPA), of which 155 (85.2%) were nonreactive and 27 (14.8%) were reactive. The 27 VITROS TPA-reactive sera were further tested with a treponemal Western blot assay (Euroimmun IgG Western Blot, EuroWB), of which 11 (41%) were indeterminate, 6 (22%) were nonreactive and 10 (37%) were reactive. Among the 10 EuroWB-reactive sera, two seroconverted to TPPA 1:80+/- after 1-year follow-up. Of 867 CIA-reactive/TRUST-reactive results, 27 (3.1%) were TPPA-nonreactive. CONCLUSIONS: The RSA identified more patients with reactive treponemal serology. However, it also yielded an increased likely false-reactive rate compared with the TSA, especially those results with low index values and TRUST-nonreactive serology, were necessary to retest with a second treponemal test. Further testing results with TPPA, VITROS TPA and EuroWB suggested the false-reactive CIA screening results and the likely false-nonreactive TPPA results when the reactive treponemal results screened with RSA were to be identified.