Lesion depth and marrow stimulation results.

AIM: The aim of this study was to study the importance Osteochondral lesion (OCL) depth as a singular factor for treatment outcomes using marrow stimulation. We hypothesized that the clinical outcomes of marrow stimulation would be inferior for lesions with depths of more than 5 mm compared to those less than 5 mm. MATERIALS & METHODS: An interventional prospective cohort study was conducted on 55 ankles in 55 patients who had been diagnosed with full-thickness osteochondral lesions of the talus; stage II, III, IV according to Anderson staging system based on magnetic resonance imaging; depth of 10 mm or less; and area of 150 mm2 or less measured by preoperative computed tomography. According to lesion depth, patients were divided into two groups: group (A) ≤ 5 mm, and group (B) ˃ 5 mm. The mean follow-up period for both groups was 30 months (range, 22-40). RESULTS: For groups A and B the average preoperative Foot and Ankle Outcome Scores (FAOS) were 43.1 ± 8.8 (range, 25-52) and 46 ± 8.5 (range, 32-60), respectively, and improved to 90 ± 4.3 (range, 80-96) (P = 0.001) and 75 ± 6.4 (range, 65-88) (P = 0.001) at the final follow-up. The average time to full weight bearing was 12 weeks (range, 10-16) in group A and 16 weeks (range, 12-20) in group B. CONCLUSIONS: Although treatment of OCLs is still undergoing changes and there are many prognostic factors that affect outcomes during marrow stimulation treatment, depth of OCL was shown to be an independent factor affecting outcomes. OCLs of less than 5 mm in depth were more likely to have superior clinical outcomes compared to OCLs of more than 5 mm. CLINICAL SIGNIFICANCE: The depth of OCL talus is an important factor as it affects the outcome of arthroscopic marrow stimulation inversely. LEVEL OF EVIDENCE: I.

Arthroscopic Wafer Procedure Versus Ulnar Shortening Osteotomy for Treatment of Idiopathic Ulnar Impaction Syndrome: A Randomized Controlled Trial.

PURPOSE: We compared the arthroscopic wafer procedure (AWP) and ulnar shortening osteotomy (USO) for treatment of idiopathic ulnar impaction syndrome in terms of clinical, functional improvement and time of return to work. METHODS: This single-center study was conducted at an academic level 1 referral center between 2014 and 2020. Sixty patients with idiopathic ulnar impaction syndrome were prospectively randomized to treatment with either AWP or USO. At the final follow-up, patients were evaluated by the Disabilities of the Arm, Shoulder, and Hand; the Modified Mayo Wrist Score; the visual analog scale for pain; wrist range of motion; and grip strength. Also, the time of return to work and complications were reported. RESULTS: The mean follow-up periods were 22 ± 5.7 months in the AWP group and 21.1 ± 5.3 months in the USO group. All patients in the USO group achieved union by 12 weeks. At the final follow-up, there were no statistically significant differences in the outcome measures (Disabilities of the Arm, Shoulder, and Hand score; Modified Mayo Wrist Score; visual analog scale score; range of motion; and grip strength) in either group. Fewer complications and an earlier return to work were observed in the AWP group. CONCLUSIONS: Both techniques yielded comparable outcomes, with earlier return to work, a lower incidence of complications, and fewer secondary procedures in the AWP group. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Outcomes of Definitive Spine Fusion Using All-pedicle-Screw Constructs in Skeletally Immature Patients Aged 8 to 10 Years With Severe Idiopathic Early-Onset Scoliosis.

BACKGROUND: The choice between growth-sparing techniques or definitive spine fusion for severe idiopathic early-onset scoliosis (IEOS) in skeletally immature patients aged 8 to 10 years represents a challenging dilemma. Although growth-sparing techniques show high complication rates in severe IEOS, the outcomes of definitive fusion in borderline skeletally immature patients with severe IEOS have not been investigated. We aimed to investigate the outcomes of early definitive fusion using all-pedicle-screw constructs in skeletally immature patients aged 8 to 10 years with severe IEOS. METHODS: The inclusion criteria were as follows: IEOS, age 8 years or above, major coronal curve ≥90 degrees, thoracic height >18 cm, no history of previous spine surgery, no intraspinal anomalies and at least 3 years of postoperative follow-up. Patients underwent instrumented spinal fusion with all-pedicle-screw constructs and multiple Ponte osteotomies. All patients completed the Scoliosis Research Society 22 revision (Arabic version) questionnaire and Body Image Disturbance Questionnaire-Scoliosis version (BIDQ-S) preoperatively and at the last follow-up. RESULTS: Fifty-five patients (24 males, 31 females; mean age: 8.96 y; range: 8 to 10 y) with severe IEOS met the inclusion criteria (mean follow-up period: 4.1±0.6 y; range: 3 to 5 y). The mean major coronal Cobb angle improved significantly (P<0.001) from 107±12.5 degrees to 26.8±6.8 degrees. Mean thoracic kyphosis improved significantly (P<0.001) from 57.2±15.8 degrees to 31.2±4.4 degrees. The loss of correction at the latest follow-up was nonsignificant. The total Scoliosis Research Society 22 revision (SRS-22r) score improved significantly from 2.5±1 to 4.3±0.7. The mean BIDQ-S score improved significantly from 4.1±0.3 to 1.6±0.3. The immediate postoperative gains in the mean thoracic height (T1-T12) and spinal height (T1-S1) were 14.9% and 19.6%, respectively, and the overall height increase at the latest follow-up was 17.8% and 23.8%, respectively. One patient underwent revision for implant failure (rod breakage). CONCLUSION: Early definitive fusion for skeletally immature patients with severe IEOS yielded excellent correction with major improvements in patient quality of life. Severe IEOS poses a significant risk, but definitive fusion can potentially mitigate that risk in patients aged 8 to 10 years.

Development of a gene signature for predicting cirrhosis risk score of chronic liver disease associated with HCV infection in Egyptians.

BACKGROUND: Complex diseases such as fibrosis are likely polygenic. Lately, cirrhosis risk score (CRS) clearly discriminated Chronic HCV patients with high-risk versus those with low-risk for cirrhosis better than clinical factors. METHODS: Herein, the CRS was assessed via genotyping by allelic discrimination assays in 243 HCV Egyptian patients categorized into 164 patients didn't develop HCC (93 mild, 71 advanced fibrosis); and 79 patients developed HCC. APRI and FIB-4 scores were calculated, compared with CRS and correlated with degree of fibrosis progression. RESULTS: Median of the three CRS, APRI and FIB-4 scores were significantly elevated in late fibrotic and HCC patients (p < 0.001); however CRS displayed proper discrimination (mild fibrosis (0.59; 0.4-0.75), advanced fibrosis (0.75; 0.7-0.86) and HCC (0.73; 0.57-0.77); (p < 0.001)). The ROC analysis of CRS score displayed modest accuracy to discriminate between mild and advanced fibrotic patient; AUC was 0.73; p < 0.0001), while AUC was only 0.57 (p = 0.05) for the discrimination between HCC and no HCC. Moreover, the combination of CRS, APRI and FIB4 lessened the power of correlation (AUC, 0.63 (p < 0.0001)) in fibrosis prognosis. In HCC prognosis, the combination of CRS, APRI and FIB4 in HCC patients showed modest accuracy with AUC, 0.59 (p = 0.0001). CONCLUSION: The diagnostic accuracy of FIB-4 for predicting liver fibrosis was nearly identical to that of CRS, however the strength of CRS score stemmed from that it is built on 7 SNPs host genetic factor. Our study validates non invasive algorithms for fibrosis prognosis purposes which may aid in decision making for therapeutic intervention.

Teres major transfer to restore external rotation of shoulder in Erb palsy patients.

BACKGROUND: The lack of external rotation and shoulder abduction as sequelae of obstetric brachial plexus palsy requires a release of the subscapularis muscle associated with tendon transfer of the internal rotator of the shoulder. The aim of this study was to present the results of a teres major transfer to the infraspinatus tendon. METHODS: This study included 20 patients (9 boys and 11 girls) with a mean age of 3 years 8 months (range, 1.5-14 years). The average follow-up time was 42 months (range, 12-48 months) to determine whether external rotation weakness and internal rotation contracture sequelae were managed by anterior release of the subscapularis and teres major tendon transfer to the infraspinatus tendon. RESULTS: We found marked improvement in shoulder abduction from 67° before surgery to 158° after surgery. We also found marked improvements in active external rotation from 8° before surgery to 85° after surgery and in passive external rotation from 0° preoperatively to 72° postoperatively. Two cases showed a loss of the last degrees of internal rotation, but this improved after physiotherapy. CONCLUSIONS: Anterior release of the subscapularis tendon with a teres major transfer to the infraspinatus tendon significantly improves shoulder function in Erb palsy patients with internal rotation contracture.

Scaphoid excision with lunatocapitate fusion for the treatment of scaphoid nonunion with advanced collapsed wrist.

PURPOSE: To investigate the union rate after lunatocapitate arthrodesis for the treatment of scaphoid nonunion advanced collapse (SNAC) wrists and to evaluate the clinical results of this technique. METHODS: We conducted a prospective study between January 2014 and July 2017. Fifteen males with painful stage III SNAC wrists (average age, 32 years, range, 20-37 years; average follow-up time, 25.2 months, range, 20-36 months) underwent scaphoid excision and lunatocapitate fusion. Lunatocapitate fusions were fixed with headless Herbert screws with K-wire fixation (retrograde direction). Radiographs, wrist range of motion, and Mayo wrist score were examined. RESULTS: All patients achieved radiographic and clinical union after lunatocapitate fusion during follow-up (average 10 months post-operatively). The flexion-extension arc was 70°, and the average Mayo wrist score was 74.3 points (eight with excellent, four with good, three with satisfactory, and one with poor result). Thirteen patients returned to work, whereas two with nonunion required surgical graft revision. Complete union was achieved at an average of 12 weeks after graft revision, with improved range of motion, and the patients returned to work with a change in their occupation. CONCLUSIONS: Lunatocapitate arthrodesis is a satisfactory therapeutic alternative to four-corner fusion for SNAC wrists.

Efficacy and safety of sofosbuvir-based therapy in hepatitis C virus recurrence post living donor liver transplant: A real life egyptian experience.

BACKGROUND AND AIM: Direct acting antiviral has offered treatment of hepatitis C virus (HCV) recurrence post liver transplantation (LT) with an all-oral regimen for short duration, excellent safety profile, and high sustained virological response (SVR). The aim of this study was to evaluate the efficacy and safety of sofosbuvir (SOF)-based regimens in the real world among a cohort of Egyptian patients with recurrent HCV post living donor LT (LDLT). METHODS: Patients with HCV-G4 recurrence post-LDLT were recruited from National Committee of Control of Viral Hepatitis, Egypt, from November 2014 to May 2017. They received different SOF-based regimens according to the treatment protocols available during this period. Patients' outcome and Adverse effects (AE) were evaluated. RESULTS: One hundred ninety patients (170 males, mean age 56.8 ± 7.9 years) were included. Calcineurin inhibitors were the main immunosuppression used (173 patients). Out of 190, 119 (62.6%) received SOF/ribavirin (RBV), 38 (20%) SOF/simeprevir (SMV), 22 (11.6%) SOF/daclatasvir (DSV)/ ± RBV, and 11 (5.8%) received SOF/LDV/ ± RBV. Overall SVR12 was 89.5%, 84.9% in SOF/RBV group, 94.7% in SOF/SMV, 100% in SOF/DCV, and 100% in SOF/LDV with no statistically significant difference ( P = 0.104). The AE reported were as follows: anemia (n = 65, 34.4%) mainly in SOF/RBV group, transient hyperbilirubinemia during SOF/SMV in 13 patients (34%), mild Acute cellular rejection in eight patients (4.2%), and hepatocellular carcinoma in two patients (1%) mainly driven by underlying liver condition. Two deaths were unlikely related to HCV therapy. CONCLUSION: Different SOF-based regimens were effective with high SVR12 rates in a difficult-to-treat population, recurrent HCV post LDLT.

Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience.

BACKGROUND AND AIMS: The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources. METHODS: Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included. RESULTS: For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%. CONCLUSION: Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed. LAY SUMMARY: We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.

Double-bundle anterior cruciate ligament reconstruction is better than single-bundle reconstruction in terms of objective assessment but not in terms of subjective score.

PURPOSE: A comparison of clinical outcomes between double-bundle (DB) and single-bundle (SB) anterior cruciate ligament (ACL) reconstruction for patients with ACL injury. METHODS: Sixty patients were treated with either SB (n = 30) or DB (n = 30) ACL reconstruction between 2011 and 2012. The hamstring tendons were autografted with suspensory fixation on the femoral side, while a bio-absorbable interference screw was used for fixation on the tibial side. These patients were evaluated using Lysholm score, International Knee Documentation Committee (IKDC) forms (both objective and subjective), Lachman test, pivot shift test, and KT 1000 arthrometer. RESULTS: After a median follow-up duration of 35.5 months (ranging between 30 and 42 months), the frequency of patients who had high objective IKDC scores was significantly higher in the DB group than those in the SB group. In terms of DB, the Lachman test was normal in 26 patients (86.7%), nearly normal in three patients (10%), and abnormal in one patient (3.3%); comparatively, in terms of SB, the Lachman test was normal in 20 patients (66.7%), nearly normal in eight patients (26.7%) and abnormal in two patients (6.6%). The pivot shift test was negative in 29 patients (96.7%) and 21 patients (70%) for DB and SB, respectively. The average KT-1000 side-to-side difference was 1.0 mm for DB and 1.5 mm for SB. The subjective IKDC and Lysholm score showed non-significant differences between both techniques. CONCLUSION: Double-bundle ACL reconstruction was found to have a significant advantage in anterior and rotational stability as well as objective IKDC than that of SB reconstruction. However, subjective measurements showed no statistical differences between the techniques. LEVEL OF EVIDENCE: II.

Temperament and self-based correlates of cooperative, competitive and individualistic learning preferences.

People vary in the extent to which they prefer cooperative, competitive or individualistic achievement tasks. In this research, we conducted two studies designed to investigate correlates and possible roots of these social interdependence orientations, namely approach and avoidance temperament, general self-efficacy, implicit theories of intelligence, and contingencies of self-worth based in others' approval, competition and academic competence. The results indicated that approach temperament, general self-efficacy and incremental theory were positively related, and entity theory was negatively related to cooperative preferences (|r| range from .11 to .41); approach temperament, general self-efficacy, competition contingencies and academic competence contingencies were positively related to competitive preferences (|r| range from .16 to .46); and avoidance temperament, entity theory, competitive contingencies and academic competence contingencies were positively related, and incremental theory was negatively related to individualistic preferences (|r| range from .09 to .15). The findings are discussed with regard to the meaning of each of the three social interdependence orientations, cultural differences among the observed relations and implications for practitioners.

Microwave ablation versus transarterial chemoembolization in large hepatocellular carcinoma: prospective analysis.

OBJECTIVE: Limited therapies are offered for large hepatocellular carcinoma (HCC). It carries dismal prognosis and efforts tried changing its management from a palliative to a curative mode. Transarterial chemoembolization (TACE) is a palliative procedure that may have survival benefit if compared to non-management of large lesions. Microwave ablation (MWA) has emerged as a relatively new technique with promise of larger and faster ablation. We aim to evaluate the efficacy and safety of percutaneous MWA versus TACE for large tumors (5-7 cm) and to assess their effects on local tumor progression and survival. PATIENTS AND METHODS: Sixty-four patients with large lesions are managed in our multidisciplinary HCC clinic and were divided into two groups treated either by MWA or TACE. Complete response rate, local recurrence, de novo lesions, and overall survival analysis are compared between both procedures. RESULTS: Both groups were comparable as regards the demographic and ultrasonographic features. MWA showed higher rates of complete ablation (75%) with fewer sessions, lower incidence of tumor recurrence (p = 0.02), development of de novo lesions (p = 0.03), occurrence of post-treatment ascites (p = 0.003), and higher survival rates (p = 0.04). The mean survival of the microwave group was 21.7 months with actuarial probability of survival at 12 and 18 months 78.2% and 68.4%, respectively. The mean survival of the TACE group was 13.7 months with actuarial probability of survival at 12 and 18 months being 52.4% and 28.6%, respectively. CONCLUSION: MWA showed better results than TACE in the management of large HCC lesions.

Efficacy and survival analysis of percutaneous radiofrequency versus microwave ablation for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary tumor of the liver with poor prognosis. For early stage HCC, treatment options include surgical resection, liver transplantation, and percutaneous ablation. Percutaneous ablative techniques (radiofrequency and microwave techniques) emerged as best therapeutic options for nonsurgical patients. AIMS: We aimed to determine the safety and efficacy of radiofrequency and microwave procedures for ablation of early stage HCC lesions and prospectively follow up our patients for survival analysis. PATIENTS AND METHODS: One Hundred and 11 patients with early HCC are managed in our multidisciplinary clinic using either radiofrequency or microwave ablation. Patients are assessed for efficacy and safety. Complete ablation rate, local recurrence, and overall survival analysis are compared between both procedures. RESULTS: Radiofrequency ablation group (n = 45) and microwave ablation group (n = 66) were nearly comparable as regards the tumor and patients characteristics. Complete ablation was achieved in 94.2 and 96.1% of patients managed by radiofrequency and microwave ablation techniques, respectively (p value 0.6) with a low rate of minor complications (11.1 and 3.2, respectively) including subcapsular hematoma, thigh burn, abdominal wall skin burn, and pleural effusion. Ablation rates did not differ between ablated lesions ≤ 3 and 3-5 cm. A lower incidence of local recurrence was observed in microwave group (3.9 vs. 13.5% in radiofrequency group, p value 0.04). No difference between both groups as regards de novo lesions, portal vein thrombosis, and abdominal lymphadenopathy. The overall actuarial probability of survival was 91.6% at 1 year and 86.1% at 2 years with a higher survival rates noticed in microwave group but still without significant difference (p value 0.49). CONCLUSION: Radiofrequency and microwave ablations led to safe and equivalent ablation and survival rates (with superiority for microwave ablation as regards the incidence of local recurrence).

Virtual Screening and Biological Evaluation of Potential PD-1/PD-L1 Immune Checkpoint Inhibitors as Anti-Hepatocellular Carcinoma Agents.

Blockade of the programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) immune checkpoint pathway is an efficient immunotherapeutic modality that provided significant advances in cancer treatment especially in solid tumors highly resistant to traditional therapy. Monoclonal antibodies (mAbs) and small-molecule inhibitors are the two main strategies used to block this axis with mAbs suffering from many limitations. Accordingly, the current alternative is the development of small-molecule PD-1/PD-L1 inhibitors. Here, we present a sequential virtual screening (VS) protocol involving pharmacophore screening followed by molecular docking for the discovery of novel PD-L1 inhibitors. The VS protocol resulted in the discovery of eight novel compounds. A 100 ns MD simulation showed two compounds, H4 and H6, exhibiting a stable binding mode at the PD-L1 dimer interface. Upon evaluation of their immunological activities, the two compounds induced higher cytokines levels (IL-2, IL-6, and INF-γ) relative to BMS-202, 72 h post treatment of PBMCs of HCC patients. Thus, the discovered hits represent potential leads for the development of novel classes targeting the PD-L1 receptor as anti-hepatocellular carcinoma agents.

Dual Mobility Cup in Fractures of the Femoral Neck in Neuromuscular Disorders and Cognitive Dysfunction Patients above 60 years-old.

Objectives: Dislocation rate of total hip arthroplasty (THA) can be as high as 20% for patients with fracture neck of femur, which is a disastrous complication in these vulnerable patients. Numerous techniques, including bipolar arthroplasty and constrained liner, have been adopted to minimize the risk of dislocation. We aimed to evaluate the role of dual mobility Cups in treating patients with fractures of the femoral neck with high risk of postoperative dislocation due to neuromuscular instability disorders. Methods: A prospective cohort study was conducted (place is blinded as asked during submission), between 2016 and 2019, with a post-operative follow up period of two years. We included skeletally mature patients with femoral neck fractures having neuromuscular disorders and cognitive dysfunction who are candidates for THA above 60 years. Patients were then followed up clinically and radiographically at the clinic using Harris Hip Score (HHS) and x-rays at six weeks, six months, one year and two years postoperatively. Results: Twenty patients (20 hips) with femoral neck fractures with high risk of postoperative dislocation due to neuromuscular instability disorders undergoing dual mobility cup were included. The mean age of patients was 70.5 ±6.42 years. There is highly significant difference between HHS preoperatively and postoperatively (six weeks, six months and one, two years) p<0.001.Infection occurred in one case (5 %), sciatic nerve injury occurred in one case (5%), and none of the patients had postoperative dislocation. Conclusion: Dual mobility cup is effective in preventing early dislocation in patients suffered from fracture neck of femur with muscle weakness due to neurologic disorders.

Africa Guidelines for Hepatocellular Carcinoma Buildup Process.

PURPOSE: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

P53 is a risk factor of de-novo hepatitis C-related hepatocellular carcinoma treated with direct-acting antivirals: a case-control study.

BACKGROUND: The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP). METHOD: This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA). RESULTS: Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0-2.1) in liver cirrhosis and 2.2 (2.0-2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis. CONCLUSION: P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.

Seven gene signature explores the impact of DAAs on the appearance of hepatocellular carcinoma in HCV infected patients.

HCV damages the hepatocytes ending with hepatocellular carcinoma (HCC). The direct-acting antivirals (DAAs) treatment has raised hopes for reducing the incidence of HCC. However, several scientific debate regarding the impact of DAAs on the occurrence of HCC in patients with cirrhosis. We aimed to study the Cirrhosis Risk Score (CRS), several clinical factors and tumor characteristics between patients who developed HCC either with or without DAAs treatment "DAA-exposed HCC patients" and "DAA-unexposed HCC patients". Methods: CRS was assessed via genotyping by allelic discrimination assays in HCV patients who developed de novo HCC (with DAAs (DAA-exposed HCC patients, n = 50), and without DAAs treatment (DAA-unexposed HCC patients, n = 40)). APRI, FIB-4 scores, and tumor characteristics were assessed. Results: Around 60% and 48% of DAA-exposed HCC patients and DAA-unexposed HCC patients; respectively had high CRS scores without significant difference. DAA-exposed HCC patients showed elevated Albumin, Hemoglobin and decreased ALT, AST compared with DAA-unexposed HCC patients (P = 0.002, 0.04, <0.001 and 0.006; respectively). FIB4 and APRI didn't reach the statistical difference between the studied groups. DAA-exposed HCC patients have higher overall survival (OS) than DAA-unexposed HCC patients (median: 30 & 15 months; respectively (p = 0.019)). Moreover, no significant differences were observed between the two groups in their focal lesion characteristics. Conclusion: All studied patients are genetically predisposed to develop HCC. Moreover, DAAs significantly improved the OS and the biochemical parameters. No differences between the two groups were detected regarding their tumor characteristics. Accordingly, the appearance of HCC after treatment is attributed to the natural course of cirrhosis.

Plasma cell-free DNA integrity index and hepatocellular carcinoma treated or not with direct-acting antivirals: A case-control study.

BACKGROUND AND STUDY AIMS: The clinical value of the cell-free DNA (cf-DNA) integrity index as a diagnostic biomarker of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) was investigated and correlated with alpha-fetoprotein (AFP). PATIENTS AND METHODS: This case-control study was conducted on 160 patients with HCV genotype 4-related liver cirrhosis. Group 1 consisted of 80 patients with HCC, including 40 patients naïve to direct-acting antivirals (DAAs) and 40 patients who received DAAs and achieved sustained virological response. Group 2 comprised 80 patients with cirrhosis without HCC. Plasma cf-DNA integrity index using ALU 115 and ALU 247 sequences was assessed using SYBR Green-based real-time polymerase chain reaction (RT-PCR). The cf-DNA integrity index was calculated as the ratio of Q247/Q115 where Q115 and Q247 are the ALU-qPCR results obtained using ALU 115 and ALU 247, respectively. RESULTS: Patients with HCC had significantly lower plasma cf-DNA integrity index than those with liver cirrhosis. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those who did not. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve of 0.965 and 0.886 for detecting HCC using the cf-DNA integrity index and AFP, respectively. The combination of the cf-DNA integrity index and AFP improved the sensitivity from 81.6% to 94.7%, positive predictive value from 93.4% to 94.7%, negative predictive value from 84.4% to 94.9%, and accuracy from 88.4% to 94.8%. CONCLUSION: The cf-DNA integrity index can predict the occurrence of HCV genotype 4-related HCC. No significant difference in the cf-DNA integrity index was observed between patients with HCC who received DAAs and those without previous DAAs. The combination of the cf-DNA integrity index and AFP provides better HCC prediction accuracy.

Comparison of latissimus dorsi tendon transfer with subscapularis release versus sliding of internal rotation contracture in obstetrical brachial plexus paralysis sequela.

BACKGROUND: The purpose of this study was to compare the functional results of latissimus dorsi (LD) tendon transfer with those of subscapularis (SS) muscle release versus sliding. METHODS: Fifty-six patients with internal rotation contracture and external rotation (ER) weakness as sequelae of Erb's palsy were included in the study. Of the patients, 24 were included in group 1 (11 boys and 13 girls), with a mean age of 2 years 8 months (range 1.5-5 years) and a follow-up period of 62 months (range 38-68 months). The patients in group 1 underwent LD tendon transfer, with internal rotation contracture and SS release procedures. Thirty-two patients were included in group 2 (18 boys and 14 girls), with a mean age of 2 years 6 months (range 1.5-4.8 years) and a follow-up period of 58 months (range 38-68 months). The patients in group 2 underwent LD tendon transfer with SS sliding. RESULTS: A significant improvement in preoperative passive ER from - 3.6° to 67.3° after operation was observed in group 1. In group 2, preoperative passive ER in adduction improved from 0° to 72.3°. We found no significant difference (P = 0.1) in postoperative improvement in active ER in both groups (group 1 vs. group 2: 75° vs. 77.3°). Similarly, no significant difference (P = 0.7) in postoperative improvement in passive ER was found between the groups (group 1 vs. group 2: 71° vs. 72.3°). CONCLUSIONS: LD tendon transfer with SS release or sliding is an effective procedure to improve shoulder ER in patients with OBPP, with no inferiority of SS muscle release or sliding for internal rotation contractures and increased passive range of shoulder motion. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Comparison; Treatment Study.

Meta-learning algorithm development to predict outcomes in patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND AND STUDY AIMS: Prediction of prognosis and treatment outcomes for patients with hepatocellular carcinoma (HCC) is complex for most patients. Machine learning predictive analysis can be used to explore the rich information in electronic health records to discover hidden patterns and relationships. We aimed to develop a noninvasive algorithm for predicting outcome treatment options for patients with HCC. PATIENTS AND METHODS: This cross-sectional study included 1298 patients with Hepatitis C virus-related HCC attending an HCC multidisciplinary clinic, Kasr Al-Aini Hospital, Cairo University, between 2009 and 2016. Using machine learning analysis, we constructed Reduced Error Pruning (REP) decision tree algorithms and applied Auto-WEKA to select the best classifier out of 39 algorithms. RESULTS: The REP-tree algorithm predicted HCC management outcomes with a recall (sensitivity) of 0.658 and a precision (specificity) of 0.653 using only routine data. 854 (65.8%) instances were correctly identified, and 444 (34.2%) instances were incorrectly classified. Out of 31 attributes, liver decompensation was selected by REP-tree as the best predictor of HCC outcome (root node). With Auto-WEKA, the random subspace classifier was chosen as the best predictive algorithm with a recall (sensitivity) of 0.750 and a precision (specificity) of 0.75. There were 974 (75%) correctly classified instances and 324 (25%) incorrectly classified instances, which was better than REP-tree. CONCLUSION: Machine learning analysis explores data to discover hidden patterns and trends and enables the development of models to predict HCC treatment outcomes utilizing simple laboratory data. The random subspace classifier predicted the outcome more accurately than REP-tree.