Publications by authors named "Hamdan Alghamdi"

40 Publications

Favorable response to carbamazepine therapy in genetically proven myoclonus-dystonia child.

Ital J Pediatr 2021 Feb 15;47(1):33. Epub 2021 Feb 15.

Department of internal medicine, Taif University, Taif, Kingdom of Saudi Arabia.

Background: Myoclonus dystonia (MDS) is a dominantly inherited genetic disorder caused by loss-of-function mutations in the epsilon sarcoglycan gene (SGCE).

Case Presentation: We here in report a twenty months old Saudi boy who presented to us with a concern that the child is unable to walk properly. On assessment, he was flexing his left arm and left leg that usually followed by a back-ward fall. Diagnosis of dystonia induced with initiation of movement was suggested that later on proven genetically to be pathogenic mutation of sarcoglycan gene. Carbamazepine therapy was initiated with dramatic response. Response was maintained at 4 years follow up.

Conclusions: Our patient and the other previously reported cases might highlight the response of SGCE mutations to carbamazepine therapy.
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http://dx.doi.org/10.1186/s13052-021-00986-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885206PMC
February 2021

Histological and Histomorphometric Analyses of Bone Regeneration in Osteoporotic Rats Using a Xenograft Material.

Materials (Basel) 2021 Jan 5;14(1). Epub 2021 Jan 5.

Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

We evaluated the effect of osteoporotic induction after eight weeks of initial healing of bone defects grafted with a xenograft material in a rat model. Bone defects were created in the femoral condyles of 16 female Wistar rats (one defect per rat). The defects were filled with bovine bone (Inter-Oss) granules. After eight weeks of bone healing, rats were randomly ovariectomized (OVX) or sham-operated (SHAM). At 14 weeks of bone healing, all animals were euthanized. Bone specimens were harvested and processed for histological and histomorphometric analyses to assess new bone formation (N-BF%), remaining bone graft (RBG%) and trabecular bone space (Tb.Sp%) within the defect area. After 14 weeks of bone healing, histological evaluation revealed a significant alteration in trabecular bone in OVX rats compared to SHAM rats. There was lower N-BF% in OVX rats (22.5% ± 3.0%) compared to SHAM rats (37.7% ± 7.9%; < 0.05). Additionally, the RBG% was significantly lower in OVX (23.7% ± 5.8%) compared to SHAM (34.8% ± 9.6%; < 0.05) rats. Finally, the Tb.Sp% was higher in OVX (53.8% ± 7.7%) compared to SHAM (27.5% ± 14.3%; < 0.05) rats. In conclusion, within the limitations of this study, inducing an osteoporotic condition in a rat model negatively influenced bone regeneration in the created bone defect and grafted with a xenograft material.
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http://dx.doi.org/10.3390/ma14010222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795077PMC
January 2021

Histomorphometric Evaluation of Peri-Implant Bone Response to Intravenous Administration of Zoledronate (Zometa) in an Osteoporotic Rat Model.

Materials (Basel) 2020 Nov 20;13(22). Epub 2020 Nov 20.

Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia.

We evaluated the response to peri-implant bone placed in the femoral condyle of osteoporotic rats, following intravenous zoledronate (ZOL) treatment in three settings: pre-implantation (ZOL-Pre), post-implantation (ZOL-Post), and pre- + post-implantation (ZOL-Pre+Post). Twenty-four female Wistar rats were ovariectomized (OVX). After 12 weeks, the rats received titanium implants in the right femoral condyle. ZOL (0.04 mg/kg, weekly) was administered to six rats 4 weeks pre-implantation and was stopped at implant placement. To another six rats, ZOL was given post-implantation and continued for 6 weeks. Additional six rats received ZOL treatment pre- and post-implantation. Control animals received weekly saline intravenous injections. At 6 weeks post-implantation, samples were retrieved for histological evaluation of the percentage of bone area (%BA) and of the percentage of bone-to-implant contact (%BIC). BA% for ZOL-Pre (29.6% ± 9.0%) and ZOL-Post (27.9% ± 5.6%) rats were significantly increased compared to that of the controls (17.3% ± 3.9%, < 0.05). In contrast, ZOL-Pre+Post rats (20.4% ± 5.0%) showed similar BA% compared to Saline controls ( = 0.731). BIC% revealed a significant increase for ZOL-Post (65.8% ± 16.9%) and ZOL-Pre+Post (68.3% ± 10.0%) rats compared with that of Saline controls (43.3% ± 9.6%, < 0.05), while ZOL-Pre rats (55.6% ± 19%) showed a BIC% comparable to that of Saline controls ( = 0.408). Our results suggest that receiving intravenous ZOL treatment before or after implant placement enhances peri-implant bone responses in terms of bone area. However, the effect of different ZOL treatment regimens on BIC% was found to be inconclusive.
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http://dx.doi.org/10.3390/ma13225248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699926PMC
November 2020

Impact of Single or Combined Drug Therapy on Bone Regeneration in Healthy and Osteoporotic Rats.

Tissue Eng Part A 2020 Oct 23. Epub 2020 Oct 23.

Department of Periodontics and Community Dentistry and College of Dentistry, King Saud University, Riyadh, Saudi Arabia.

Complications in bone regeneration in patients with systemic impaired bone metabolism (e.g., osteoporosis) represent a rapidly increasing clinical challenge. Alendronate and simvastatin are drugs commonly used to promote bone metabolism in osteoporotic conditions. The aim of this study was to evaluate initial bone regeneration within osseous defects grafted with beta-tricalcium phosphate (β-TCP) in adjunction with systemic coadministrations of alendronate and simvastatin (i.e., daily subcutaneous injection for 3 weeks) in healthy and osteoporotic rats. Eighty Wistar female rats were ovariectomized (OVX;  = 40) or sham operated ( = 40). Six weeks later, osseous defects (a 3-mm critical-sized defect) were created in the left femoral condyles and then grafted with β-TCP. From the day following graft installation, OVX and sham animals received for 3 weeks a daily subcutaneous injection of alendronate (50 μg/kg of body weight) and simvastatin (5 mg/kg of body weight), alone or in combination. A control group was included, which received subcutaneous saline administration. At the end of the 3 weeks, rats were euthanized and specimens (femoral condyles) were retrieved for histological evaluation and histomorphometric measurements, that is, bone area (BA%) and remaining bone graft (RBG%). In osteoporotic rats, 3 weeks of daily subcutaneous injection of combined therapy (alendronate plus simvastatin) led to a significant ( < 0.05) increase in BA% and a significant decrease in RBG% compared to healthy controls in osseous defects grafted with β-TCP (BA%: 28.6 ± 12.0 vs. 18.2 ± 7.6, RBG% 61.3 ± 11.1 vs. 70.7 ± 7.3). No significant differences in BA% and RBG% were found in the OVX rats for single treatments. Furthermore, healthy controls showed similar BA% and RBG% upon single or combined therapy compared to nontreated control rats. Daily coinjections (for 3 weeks) of alendronate plus simvastatin result in a significant enhancement of bone regeneration within osseous defects grafted with β-TCP in osteoporotic rats. Despite the expected effects on osteoporotic bone, our study did not confirm the hypothesized benefit of alendronate and simvastatin on bone regeneration in osseous defects in healthy conditions. The efficacy of the combination drug therapy on bone regeneration demands further investigation to elucidate molecular and cellular aspects underlying this therapy. Impact statement Recently, increasing concerns have existed about the effect of bone diseases, such as osteoporosis, on bone regeneration. This study was to assess if antiosteoporotic single or combined drug therapy can promote bone regeneration in adjunction with bone grafting using preclinical animal models. Interestingly, the results suggest that combined therapy of alendronate plus simvastatin results in significantly increased bone regeneration within osseous defects grafted with beta-tricalcium phosphate in osteoporotic rats during a three-week healing period.
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http://dx.doi.org/10.1089/ten.TEA.2020.0122DOI Listing
October 2020

The development and future of dental implants.

Dent Mater J 2020 Mar 22;39(2):167-172. Epub 2020 Jan 22.

Department of Dentistry-Biomaterials, Radboud University Medical Center.

Since 1970s, a lot of effort has been devoted toward the development of dental implants. Dental implants are nowadays an indispensable part of clinical dentistry. The global dental implant market is expected to reach $13 billion in 2023. Although, the survival rate of dental implants has been reported above 90%, compromised bone conditions promote implant failure and endanger the current high success rates. The main concern is related to the aging population. Diabetes, osteoporosis, obesity and use of drugs are all medical conditions, which can hamper bone healing around dental implants. In view of this, research toward developing better methods of enhancing implant osseointegration have to be continued, especially in the presence of impaired bone condition. In this paper, the current changes and their future perspective are discussed.
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http://dx.doi.org/10.4012/dmj.2019-140DOI Listing
March 2020

Surface modification of pH-responsive poly(2-(tert-butylamino)ethyl methacrylate) brushes grafted on mesoporous silica nanoparticles.

Des Monomers Polym 2019 11;22(1):226-235. Epub 2019 Dec 11.

King Abdulaziz City for Science and Technology, Riyadh, Kingdom of Saudi Arabia.

Poly(2‑(tert-butylamino)ethyl methacrylate) brushes (PTBAEMA) are grown from mesoporous silica nanoparticles via surface-initiated atom transfer radical polymerization (SI-ATRP). Linear PTBAEMA brushes are protonated and highly swollen at low pH; brushes are collapsed at pH higher than 7.7 due to deprotonation, as determined by dynamic light scattering (DLS). Quaternization of these brushes is conducted using 2-iodoethanol in alkali media. DLS measurement of nanoparticles shows that surface-confined quaternization occurs and produces pH-responsive brushes with a hydrophobic upper surface. Variation of the 2-iodoethanol reaction time enables the mean degree of surface quaternization. The pH-responsive behaviour of quaternized PTBEAMA brushes at 1 h reaction time indicates low degrees of surface quaternization, dictated by the spatial location of 2-iodoethanol. Almost uniformly quaternized brushes prepared when the conducted for 3 h and became less swollen at low pH than brushes that conducted for 1 h. The intensity of the C - C - O component (286.5 eV) in the C1s X-ray photoelectron spectrum increased, suggesting that the reaction with iodoethanol was successful occurred.
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http://dx.doi.org/10.1080/15685551.2019.1699727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913628PMC
December 2019

Evaluation of Peri-Implant Bone Grafting Around Surface-Porous Dental Implants: An In Vivo Study in a Goat Model.

Materials (Basel) 2019 Nov 3;12(21). Epub 2019 Nov 3.

Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.

Dental implants with surface-porous designs have been recently developed. Clinically, peri-implant bone grafting is expected to promote early osseointegration and bone ingrowth when applied with surface-porous dental implants in challenging conditions. The aim of this study was to comparatively analyze peri-implant bone healing around solid implants and surface-porous implants with and without peri-implant bone grafting, using biomechanical and histomorphometrical assessment in a goat iliac bone model. A total of 36 implants (4.1 mm wide, 11.5 mm long) divided into three groups, solid titanium implant (STI; = 12), porous titanium implants (PTI; = 12) and PTI with peri-implant bone grafting using biphasic calcium phosphate granules (PTI + BCP; = 12), were placed bilaterally in the iliac crests of six goats. The goats were sacrificed seven weeks post-operatively and then subjected to biomechanical ( = 6 per group) and histomorphometrical ( = 6 per group) assessment. The biomechanical assessment revealed no significant differences between the three types of implants. Although the peri-implant bone-area (PIBA%) measured by histomorphometry (STI: 8.63 ± 3.93%, PTI: 9.89 ± 3.69%, PTI + BCP: 9.28 ± 2.61%) was similar for the three experimental groups, the percentage of new bone growth area (BGA%) inside the porous implant portion was significantly higher ( < 0.05) in the PTI group (10.67 ± 4.61%) compared to the PTI + BCP group (6.50 ± 6.53%). These data demonstrate that peri-implant bone grafting around surface-porous dental implants does not significantly accelerate early osseointegration and bone ingrowth.
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http://dx.doi.org/10.3390/ma12213606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862611PMC
November 2019

Ordered Intermetallic PdBi Prepared by an Electrochemically Induced Phase Transformation for Oxygen Reduction Electrocatalysis.

ACS Nano 2019 Sep 5;13(9):10818-10825. Epub 2019 Sep 5.

Department of Materials Science and Engineering , Johns Hopkins University , Baltimore , Maryland 21218 , United States.

The synthesis of alloys with long-range atomic-scale ordering (ordered intermetallics) is an emerging field of nanochemistry. Ordered intermetallic nanoparticles are useful for a wide variety of applications such as catalysis, superconductors, and magnetic devices. However, the preparation of nanostructured ordered intermetallics is challenging in comparison to disordered alloys, hindering progress in material development. Herein, we report a process for converting colloidally synthesized ordered intermetallic PdBi to ordered intermetallic PdBi nanoparticles under ambient conditions by electrochemical dealloying. The low melting point of PdBi corresponds to low vacancy formation energies, which enables the facile removal of the Bi from the surface while simultaneously enabling interdiffusion of the constituent atoms via a vacancy diffusion mechanism under ambient conditions. The resulting phase-converted ordered intermetallic PdBi exhibits 11 times and 3.5 times higher mass activity and high methanol tolerance for the oxygen reduction reaction compared with Pt/C and Pd/C, respectively, which is the highest reported for a Pd-based catalyst, to the best of our knowledge. These results establish a key development in the synthesis of noble-metal-rich ordered intermetallic phases with high catalytic activity and set forth guidelines for the design of ordered intermetallic compounds under ambient conditions.
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http://dx.doi.org/10.1021/acsnano.9b06019DOI Listing
September 2019

Bone Regeneration Using Antiosteoporotic Drugs in Adjunction with Bone Grafting: A Meta-Analysis.

Tissue Eng Part B Rev 2019 12 27;25(6):500-509. Epub 2019 Nov 27.

Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.

The aim of this review was to systematically assess bone regeneration by using antiosteoporotic drugs in adjunction with bone grafting compared with controls (bone grafting without the administration of antiosteoporotic drugs). The review also evaluated statistical differences in the effect between systemic and local routes of drugs. Also, the effect of type of drugs (anticatabolic vs. anabolic) was subevaluated. PubMed and EMBASE (via OvidSP) resulted in inclusion of 60 animal studies. The studies were assessed for reporting quality and risk of bias. Outcome data from selected studies were categorized as either experimental (bone grafting with the administration of antiosteoporotic drugs) or control. Meta-analysis of selected studies was done for these outcomes: histomorphometrical bone area (BA%) and micro-CT bone volume (BV%). In this review, several animal models (52 healthy, 6 osteoporotic, and 2 both conditions) were subjected to examine the effect of antiosteoporotic drugs on bone grafting, with a predominant use of rodent species. Assessment indicates poor reporting quality and unclear risk of bias in the majority of studies. Random-effects meta-analysis revealed a significant increase in overall BA% (mean difference [MD]: 2.6, confidence interval [CI]: 2.25 to 2.92) and BV% (MD: 0.12, CI: 0.05 to 0.19) due to osteoporotic drug treatment compared with controls. For subgroups, both routes of antiosteoporotic drug administration showed similar effects on BA%. In contrast, systemic antiosteoporotic drug administration led to significantly higher BV% (MD: 6.75, CI: 5.30 to 8.19) compared with local administration (MD: 0.02, CI: -0.03 to 0.08). Further, administration of anabolic drugs significantly increased BA% (MD: 5.75, CI: 4.62 to 6.87) compared with anticatabolic drugs (MD: 1.86, CI: 1.47 to 2.26). In conclusion, both histomorphometrical and micro-CT scan analysis indicated an overall effect of using the antiosteoporotic drugs toward bone regeneration in adjunction with grafting. However, not all studies showed a positive effect and the present results need to be applied with care, as the included papers showed experimental heterogeneity for animal models. Further (pre)clinical research is warranted to explore whether drug-based strategies can be an effective adjunctive with bone grafting. Impact Statement The aim of this meta-analysis was to assess whether antiosteoporotic drugs can promote bone regeneration in adjunction with bone grafting by using preclinical animal models. Although the majority of included studies indicated poor reporting quality and unclear risk of bias, an overall positive effect of the antiosteoporotic drugs toward bone regeneration related to bone grafts can be highlighted.
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http://dx.doi.org/10.1089/ten.TEB.2019.0132DOI Listing
December 2019

Greater prevalence of comorbidities with increasing age: Cross-sectional analysis of chronic hepatitis B patients in Saudi Arabia.

Saudi J Gastroenterol 2019 May-Jun;25(3):194-200

Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia.

Background/aims: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia.

Patients And Methods: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID).

Results: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1-12%) and cirrhosis (range 5-23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1-2% in 2010/2012).

Conclusions: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.
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http://dx.doi.org/10.4103/sjg.SJG_447_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526730PMC
April 2020

Clinical and virological outcomes of entecavir therapy in patients with chronic hepatitis B: A real life experience.

J Infect Chemother 2019 Jan 23;25(1):12-16. Epub 2018 Oct 23.

King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; Gastroenterology Division, Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia.

Background: Entecavir (ETV) is a nucleoside analogue (NA) that is effective for treatment of chronic hepatitis B (CHB) due to its low resistance rates and potent antiviral effects. We aimed to evaluate the clinical, biochemical and virological response to ETV in patients without a prior use of nucleos(t)ide (NA-naïve) vs. those who failed prior NA use (NA-experienced) in the treatment of CHB.

Methods: Patients treated between April 2012 and December 2017 were retrospectively studied. A comparison was made between patients treated with ETV in NA-naïve Vs. NA-experienced. Complete virological response (CVR) was defined as achieving undetectable HBV-DNA level, up to 15 IU/ml, partial virological response (PVR) as 15-200 IU/ml and >200 IU/ml for no virological response (NVR) after one year of therapy.

Results: Overall, 148 patients were included (69 NA-naïve and 79 NA-experienced). In NA-naïve group, 51%, 17% and 32% achieved CVR, PVR and NVR vs. 17%, 9% and 75% in NA-experienced group, respectively (p < 0.001). HBsAg seroconversion was achieved in 5.8% in NA-naïve group vs. 6.3% in NA-experienced group (p = 1.00). HBeAg seroconversion was 17% in NA-naïve group and 25% in NA-experienced group (p = 0.24). There was no significant difference in alanine transaminase normalization or in mortality rate between both groups; p = 0.87 and p = 1.00 respectively.

Conclusion: ETV therapy in CHB results in a better virological response in NA-naïve patients compared to NA-experienced. There were no differences between both groups in regards to the rate of HBsAg or HBeAg seroconversions, biochemical improvements or mortality.
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http://dx.doi.org/10.1016/j.jiac.2018.09.014DOI Listing
January 2019

Clinicopathologic characteristics andoutcomes of hepatocellular carcinoma associated with chronic hepatitis B versus hepatitis C infection.

Ann Saudi Med 2018 Sep-Oct;38(5):358-365

Dr. Abdulrahman Aljumah, Hepatology Division, Department of Hepatobiliary Sciences and Organ Transplant Center,, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences,, Ministry of National Guard Affairs,, PO Box 225264, Riyadh 11324, Saudi Arabia, T: +966-50-5411910, ORCID: http://orcid.org/0000-0002-6156.4921.

Background: Hepatocellular carcinoma (HCC) is a primary liver malignancy and one of the most common cancers worldwide. Few studies in Saudi Arabia have compared the clinicopathologic characteristics of HCC caused by hepatitis B virus (HBV) versus hepatitis C virus (HCV) and their effect on patient survival and prognosis.

Objectives: Identify differences in clinicopathological characteristics and outcomes of hepatocellular carcinoma (HCC) caused by HBV versus HCV.

Design: A retrospective medical records review.

Setting: Tertiary medical center in Riyadh.

Patients And Methods: We included all new cases of HCC with underlying HBV and HCV infection diagnosed between January 2013 and September 2017 that met inclusion criteria.

Main Outcome Measures: Clinical, biochemical, pathological and radiological characteristics, and survival differences were compared between HCC that developed in HBV- and HCV-infected patients.

Sample Size: Of 253 patients evaluated, 172 patients were included in the study.

Results: Of the 172 patients, 110 (64%) had HCV-associated HCC and 62 (36%) had HBV-associated HCC. More patients with HBV infection were males (P=.003) and were younger (P=.015) than HCV patients. HCV-infected patients who developed HCC had more advanced cirrhosis (P=.048). The prevalence of comorbidities and pre-existing cir.rhosis was similar in both groups. Seven patients (6.8%) with underlying HCV developed HCC in the absence of cirrhosis. Patients with HBV-associated HCC were less likely to meet Milan criteria at initial diagnosis than those with HCV-associated HCC (33.9% vs. 52.7%, respectively, P=.017). HBV-associated HCC occurred at a more advanced Barcelona Clinic Liver Cancer stage. The overall median survival and treatment outcome for each modality was comparable.

Conclusions: HBV- and HCV-associated HCC have distinct clinical and pathological characteristics, necessitating different screening policies to optimize HCC surveillance and management. However, viral etiology did not affect the treatment outcome and long-term survival.

Limitations: Conducted in a single-center, retrospective and lacks information about the use of antiviral treatment.

Conflict Of Interest: None.
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http://dx.doi.org/10.5144/0256-4947.2018.358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180214PMC
January 2019

Antiosteoporotic Drugs to Promote Bone Regeneration Related to Titanium Implants: A Systematic Review and Meta-Analysis.

Tissue Eng Part B Rev 2019 04 26;25(2):89-99. Epub 2018 Oct 26.

1 Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.

Impact Statement: This meta-analysis was to investigate literature on the administration of antiosteoporotic drugs as an effective adjunct therapy for implant osseointegration using animal models.
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http://dx.doi.org/10.1089/ten.TEB.2018.0120DOI Listing
April 2019

Biomarkers as Independent Predictors of Bone Regeneration around Biomaterials: A Systematic Review of Literature.

J Contemp Dent Pract 2018 May 1;19(5):605-618. Epub 2018 May 1.

Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia; Research Support Unit, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia, Phone: +966114677732, e-mail:

Background: Biomarkers are detected during bone formation and resorption associated with the dynamics of bone metabolism and are gaining importance as preferential indicators of bone healing in comparison with conventional methodologies. Current literature suggests that the usage of bone turnover markers for monitoring bone regeneration in association with biomaterials is limited.

Aim: To systematically review literature and evaluate whether bone-biomarkers can independently predict bone regeneration following implantation of various bone biomaterials.

Materials And Methods: An electronic search was conducted in PubMed (MEDLINE) database from 1980 to January 2017. The articles for systematic review were selected based on formulated inclusion and exclusion criteria Results: Upon database searching, 443 articles were retrieved and thoroughly reviewed based on the inclusion and exclusion criteria. In all, 41 studies were finally included for evaluation out of which 4 were clinical studies and the remaining 37 studies utilized animal models. On further evaluation, 12 studies reported the presence of biomarkers in association with cellular response during bone regeneration around bio-materials. Moreover, biomarkers related to enzyme activity and matrix protein derivatives were enhanced during bone-matrix deposition as reported in 14 studies. Inorganic skeletal matrix biomarkers indicative of bone mineralization showed positive expression in eight studies.

Conclusion: Several biomarkers appear to be useful for the assessment of bone regeneration around biomaterials. Although biomarkers are capable of independently predicting bone regeneration, lack of substantial evidence in the literature limits their true clinical utility.

Clinical Significance: Noninvasive and inexpensive methods of isolating and characterization of biomarkers from cellular and extracellular skeletal matrix during bone regeneration have proven value in evaluating success of bone biomaterials.
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May 2018

Real life efficacy of ledipasvir/sofosbuvir in hepatitis C genotype 4-infected patients with advanced liver fibrosis and decompensated cirrhosis.

J Infect 2018 06 6;76(6):536-542. Epub 2018 May 6.

Hepatobiliary Sciences & Liver Transplantation, King Abdulaziz Medical City, Jeddah, Saudi Arabia; King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis.

Patients & Methods: This observational cohort (n = 213) included GT4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600-1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs).

Results: The mean age of the overall cohort was 59.6 ± 12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics (P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis (P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy).

Conclusion: LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.
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http://dx.doi.org/10.1016/j.jinf.2018.04.001DOI Listing
June 2018

Methods to Improve Osseointegration of Dental Implants in Low Quality (Type-IV) Bone: An Overview.

J Funct Biomater 2018 Jan 13;9(1). Epub 2018 Jan 13.

Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.

Nowadays, dental implants have become more common treatment for replacing missing teeth and aim to improve chewing efficiency, physical health, and esthetics. The favorable clinical performance of dental implants has been attributed to their firm osseointegration, as introduced by Brånemark in 1965. Although the survival rate of dental implants over a 10-year observation has been reported to be higher than 90% in totally edentulous jaws, the clinical outcome of implant treatment is challenged in compromised (bone) conditions, as are frequently present in elderly people. The biomechanical characteristics of bone in aged patients do not offer proper stability to implants, being similar to type-IV bone (Lekholm & Zarb classification), in which a decreased clinical fixation of implants has been clearly demonstrated. However, the search for improved osseointegration has continued forward for the new evolution of modern dental implants. This represents a continuum of developments spanning more than 20 years of research on implant related-factors including surgical techniques, implant design, and surface properties. The methods to enhance osseointegration of dental implants in low quality (type-IV) bone are described in a general manner in this review.
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http://dx.doi.org/10.3390/jfb9010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872093PMC
January 2018

Antibacterial activity of trimetal (CuZnFe) oxide nanoparticles.

Int J Nanomedicine 2018 20;13:77-87. Epub 2017 Dec 20.

Prince Naif Health Research Center, Molecular and Cell Biology Laboratory, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Background: The increasing resistance of pathogenic bacteria to antibiotics is a challenging worldwide health problem that has led to the search for new and more efficient antibacterial agents. Nanotechnology has proven to be an effective tool for the fight against bacteria.

Methods: In this paper, we present the synthesis and traits of trimetal (CuZnFe) oxide nanoparticles (NPs) using X-ray diffraction, high-resolution transmission electron microscopy, and energy dispersive x-ray spectroscopy. We evaluated the antibacterial activity of these NPs against gram-negative and gram-positive and then compared it to that of their pure single-metal oxide components CuO and ZnO.

Results: Our study showed that the antibacterial activity of the trimetal oxide NPs was greater against . than against . . Overall, the antimicrobial effect of trimetal NPs is between those of pure ZnO and CuO nanoparticles, which may mean that their cytotoxicity is also between that of pure ZnO and CuO NPs, making them potential antibiotics. However, the cytotoxicity of trimetal NPs to mammalian cells needs to be verified.

Conclusion: The combination of three metal oxide NPs (ZnO, CuO, and FeO) in one multimetal (CuZnFe) oxide NPs will enhance the therapeutic strategy against a wide range of microbial infections. Bacteria are unlikely to develop resistance against this new NP because bacteria must go through a series of mutations to become resistant to the trimetal oxide NP. Therefore, this NP can combat existing and emerging bacterial infections.
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http://dx.doi.org/10.2147/IJN.S154218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743187PMC
April 2018

Visualization of calcium phosphate cement in teeth by zero echo time H MRI at high field.

NMR Biomed 2018 02 21;31(2). Epub 2017 Nov 21.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.

H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high-field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T and T * values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T * relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T * values were 273 ± 19, 562 ± 221 and 476 ± 147 μs, respectively, the average T values were 1234 ± 27, 963 ± 151 and 577 ± 41 μs, respectively, and the average T values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal-to-noise-ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC-filled lesions showed less homogeneous structures, a lower T value and T * separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed.
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http://dx.doi.org/10.1002/nbm.3859DOI Listing
February 2018

Pharmacokinetics-Based Adjusted Versus Standard Dose of Ribavirin Does Not Improve Virologic Response Rates in Chronic Hepatitis C Genotype 4 Patients: A Randomized Controlled Trial.

J Interferon Cytokine Res 2017 11;37(11):488-493

10 Department of Pharmacology and Toxicology, CHU Limoges , Limoges, France .

Optimal doses of Ribavirin (RBV) for hepatitis C virus (HCV) treatment are not known. To assess the safety and efficacy of PegIFNalfa-2a in combination with an adjusted (ADJ) RBV dose based on early pharmacokinetics versus a fixed standard (STD) dose of RBV in chronic HCV genotype (GT) 4-naive patients in a randomized trial. One hundred eighty-one patients were randomized. The baseline variables were similar in both arms and females were 50.3% of the patients, 76.5% had minimal-moderate fibrosis (F0-2). Sustained virologic response (SVR) was achieved in 99 (54.7%) subjects. SVR was seen in 50/90 (55.6%) of ADJ dose of RBV and 49/91 (53.9%) of STD dose subjects. Prematurely withdrawal or discontinuation of treatment prematurely in the ADJ RBV arm occurred in 11/90 patients (12.2%) compared with 6/91 subjects (6.6%) in the STD arm (P = 0.214). Similarly, virologic relapse was seen in 14/90 (15.6%) patients of the ADJ arm and 12/91 (13.2%) of the STD arm. Anemia grade 3-4 was seen in 36.7% in ADJ versus 17.6% in STD arm (P = 0.003). Occurrence of rapid virologic response and absences of F4 fibrosis predicted SVR in a univariate analysis. However, age, gender, weight, presence of diabetes, baseline alanine aminotransferase, and vitamin D levels were not significantly different in patients achieving SVR. ADJ higher doses of RBV based on its early pharmacokinetics-based RBV do not improve SVR rates in HCV GT4 treated in combination with peg-IFN alpha-2-a versus STD therapy. Patients on ADJ higher doses of RBV experienced higher rates of anemia and require more erythropoietin without increasing SVR.
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http://dx.doi.org/10.1089/jir.2017.0054DOI Listing
November 2017

Effect of surface alkali-based treatment of titanium implants on ability to promote in vitro mineralization and in vivo bone formation.

Acta Biomater 2017 07 9;57:511-523. Epub 2017 May 9.

Department of Periodontics and Community Dentistry, College of Dentistry Research Center (CDRC), King Saud University, Riyadh, Saudi Arabia. Electronic address: http://www.rimls.nl/people/a/alghamdi-hamdan/.

This study investigated whether a novel alkali-based surface modification enhances in vitro mineralization as well as in vivo bone formation around titanium (Ti) implants in a femoral condyle model of 36 male Wister rats. All implant surfaces were grit-blasted and then received either acid-etching treatment, alkali-based treatment, or were left untreated (controls). Histological and histomorphometrical analyses were performed on retrieved specimens after 4 and 8weeks of healing to assess peri-implant bone formation. Results of implants surface characterisation showed notable differences in the topography and composition of alkali-treated surfaces, reflecting the formation of submicron-structured alkali-titanate layer. In the in vitro test, alkali-treated Ti surfaces showed the ability to stimulate mineralization upon soaking in simulated body fluid (SBF). In vivo histomorphometrical analyses showed similar values for bone area (BA%) and bone-to-implant contact (BIC%) for all experimental groups after both 4- and 8-week implantation periods. In conclusion, the surface topography and composition of the grit-blasted Ti implants was significantly modified using alkali-based treatment. With respect to the present in vivo model, the biological performance of alkali-treated Ti implants is comparable to the commercially available, grit-blasted, acid-etched Ti implants.

Statement Of Significance: Since success rate of dental implants might be challenged in bone of low density, an optimum implant surface characteristic is demanding. In this work, alkali treatment of Ti implants showed significant advantage of surface mineralization upon soaking in simulated body fluid. Using an in vivo rat model, Ti surfaces with either acid-etching treatment or alkali-based treatment evoked robust bone formation around Ti implants. Such information may be utilized for the advancement of biomaterials research for bone implants in future.
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http://dx.doi.org/10.1016/j.actbio.2017.05.016DOI Listing
July 2017

SASLT guidelines: Update in treatment of Hepatitis C virus infection.

Saudi J Gastroenterol 2016 Aug;22 Suppl:S25-57

Department of Medicine, Gastroenterology unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.4103/1319-3767.188067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004485PMC
August 2016

Clinical Presentation, Risk Factors, and Treatment Modalities of Hepatocellular Carcinoma: A Single Tertiary Care Center Experience.

Gastroenterol Res Pract 2016 25;2016:1989045. Epub 2016 Jul 25.

Division of Hepatology, Department of Hepatobiliary Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, P.O. Box 22490, Riyadh 11426, Saudi Arabia; King Saud bin Abdulaziz University for Health Sciences, P.O. Box 22490, Riyadh 11426, Saudi Arabia.

Objective. To investigate the risk factors, clinical characteristics, treatment modalities, and outcomes in Saudi patients with HCC and propose points for early detection of the disease. Methods. Patients were stratified according to underlying risk factors for the development of HCC. Barcelona Clinic Liver Cancer (BCLC) was used for cancer staging. Treatment was classified into surgical resection/liver transplantation; locoregional ablation therapy; transarterial embolization; systemic chemotherapy; and best supportive care. Results. A total of 235 patients were included. Males had higher tumor size and incidence of portal vein thrombosis. Viral hepatitis was a risk factor in 75.7%. The most common BCLC stages were B (34.5%) and A (33.6%), and the most common radiological presentation was a single nodule of less than 5 cm. Metastases were present in 13.2%. Overall, 77 patients (32.8%) underwent a potentially curative treatment as the initial therapy. The most commonly utilized treatment modality was chemoembolization with 113 sessions in 71 patients. The overall median survival was 15.97 ± 27.18 months. Conclusion. HCC in Saudi Arabia is associated with high prevalence of HCV. Potentially curative therapies were underutilized in our patients. Cancer stage BCLC-B was the most frequent (34.5%) followed by BCLC-A (33.6%). The overall median survival was shorter than other studies.
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http://dx.doi.org/10.1155/2016/1989045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976192PMC
August 2016

Osteogenesis around CaP-coated titanium implants visualized using 3D histology and micro-computed tomography.

J Biomed Mater Res A 2015 Nov 19;103(11):3463-73. Epub 2015 May 19.

Department of Biomaterials, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.

Calcium phosphate (CaP) coatings can enhance the performance of bone implants in compromised conditions, such as osteoporosis. Therefore, this study compared non-coated vs. CaP-coated (n = 8) titanium implants in osteoporotic ovariectomized (OVX) rats. Bone volume (BV) was assessed using micro-computer tomography (micro-CT) and three-dimensional (3D) histology, in three zones from the implant surface. Bone remodeling was assessed using fluorochrome labels and osteoclast staining. Micro-CT and 3D histology showed a BV reduction in OVX animals, of respectively 22.4 and 10.5%. BV was significantly increased inside all zones around CaP coatings, especially in the inner zone of the OVX animals. Fluorochrome labels were predominantly seen when the coating was applied. Osteoclasts were mainly found in the area remote from the surface of non-coated implants in control animals. For the coated implants, osteoclasts were distributed evenly, and present in direct vicinity of the surface. In conclusion, 3D histology is a suitable technique to obtain data and insight into bone architecture around implants at relatively high resolution. Bone formation was significantly reduced in osteoporotic animals. CaP coatings resulted in a higher BV directly around implants installed in osteoporotic animals, enhanced turnover, and a shift of remodeling activity toward the implant surface.
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http://dx.doi.org/10.1002/jbm.a.35485DOI Listing
November 2015

SASLT position statement on the direct-acting antiviral agents for the treatment of hepatitis C virus infection.

Saudi J Gastroenterol 2015 Mar-Apr;21(2):60-3

Division of Gastroenterology, Department of Medicine, King Abdulaziz Medical City, Jeddah; Liver Disease Research Center, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.4103/1319-3767.153810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392576PMC
January 2016

Self-healing hybrid nanocomposites consisting of bisphosphonated hyaluronan and calcium phosphate nanoparticles.

Biomaterials 2014 Aug 24;35(25):6918-29. Epub 2014 May 24.

Department of Biomaterials, Radboud University Medical Center, 6525EX Nijmegen, The Netherlands. Electronic address:

Non-covalent interactions are often regarded as insufficient to construct macroscopic materials of substantial integrity and cohesion. However, the low binding energy of such reversible interactions can be compensated by increasing their number to work in concert to create strong materials. Here we present the successful development of an injectable, cohesive nanocomposite hydrogel based on reversible bonds between calcium phosphate nanoparticles and bisphosphonate-functionalized hyaluronic acid. These nanocomposites display a capacity for self-healing as well as adhesiveness to mineral surfaces such as enamel and hydroxyapatite. Most importantly, these non-covalently cross-linked composites are surprisingly robust yet biodegradable upon extensive in vitro and in vivo testing and show bone interactive capacity evidenced by bone ingrowth into material remnants. The herein presented method provides a new methodology for constructing nanoscale composites for biomedical applications, which owe their integrity to reversible bonds.
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http://dx.doi.org/10.1016/j.biomaterials.2014.05.003DOI Listing
August 2014

Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats.

Biomaterials 2014 Jul 14;35(21):5482-90. Epub 2014 Apr 14.

Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands. Electronic address:

The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by μCT) and bone area (%BA; by histomorphometry) were significantly increased within a distance of 500 μm from implant surfaces functionalized with BP compared to control implants in osteoporotic and healthy conditions. Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The results of real-time PCR revealed similar osteogenic gene expression levels to all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP surface coatings represents an effective strategy for synergistically improvement of bone-implant integration, especially in osteoporotic conditions.
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http://dx.doi.org/10.1016/j.biomaterials.2014.03.069DOI Listing
July 2014

Osteoporotic rat models for evaluation of osseointegration of bone implants.

Tissue Eng Part C Methods 2014 Jun 26;20(6):493-505. Epub 2013 Nov 26.

1 Department of Biomaterials, Radboud University Medical Center , Nijmegen, The Netherlands .

Osseointegration of dental and orthopedic bone implants is the important process that leads to mechanical fixation of implants and warrants implant functionality. In view of increasing numbers of osteoporotic patients, bone implant surface optimization strategies with instructive and drug-loading ability have been heavily explored. However, few animal models are available to study the effect of novel implant surface modifications in osteoporotic conditions. Since laboratory rats comply with a number of practical advantages, including the reliability of several methods for rapid induction of osteoporotic conditions, the present work aimed to define the use of the femoral condyle in osteoporotic female and male rats as a suitable implantation model to study osseointegration of bone implants. The method describes the procedures for induction (by hypogonadism) and assessment (by in vivo micro-computed tomography [CT]) of osteoporotic conditions in both female and male rats. The implantation site architecture (femoral condyle bone properties and dimensions) was comparatively evaluated for female and male rats, and the implant installation procedures are described. Finally, the possible analytical techniques to evaluate bone responses via mechanical tests, ex vivo micro-CT, and histological methods are provided.
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http://dx.doi.org/10.1089/ten.TEC.2013.0327DOI Listing
June 2014

Predictors of significant fibrosis in chronic hepatitis B patients with low viremia.

J Clin Gastroenterol 2014 Jul;48(6):e50-6

*College of Medicine, Liver Disease Research Center, King Saud University †Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, AB, Canada ‡Department of Gastroenterology, Riyadh Military Hospital, Riyadh §Department of Medicine, Division of Gastroenterology, King Fahad General Hospital, Jeddah ∥Department of Medicine, Division of Gastroenterology ¶Department of Pathology, King Faisal Specialist Hospital & Research Center Departments of #Pathology **Hepatobiliary Sciences & Liver Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Background And Aim: The data on the prevalence and predictors of significant fibrosis (≥F2, METAVIR) in chronic hepatitis B virus (HBV) patients with low viremia are limited. We aimed to assess both the prevalence predictors of ≥F2 fibrosis in hepatitis B envelope antigen-negative patients with HBV DNA <20,000 IU/mL.

Methods: Hepatitis B envelope antigen-negative patients (n=213) with mean HBV DNA <2000 IU/mL (n=97) and HBV DNA 2000 to 20,000 IU/mL (n=116) were included and all had liver biopsy. Variables significantly associated with ≥F2 fibrosis on an univariate analysis were included in a multivariate logistic regression model.

Results: Overall, 40 (18.8%) patients had ≥F2 fibrosis, with no difference between those with mean HBV DNA <2000 IU/mL (19.6%) compared with patients with HBV DNA of 2000 to 20,000 IU/mL (18.1%; P=0.782). Fibrosis ≥F2 was similar in patients with HBV DNA <2000 versus 2000 to 20,000 IU/mL in relation to varying alanine aminotransferase thresholds (P>0.05), and was less frequent in persistently normal alanine aminotransferase patients (13.6%) when compared with those with elevated or fluctuating levels (25.3%, P=0.030). Fewer patients under 40 years of age had ≥F2 fibrosis (12.5%) as compared with older ones (28.2%; P=0.004). Logistic regression analysis identified higher aspartate aminotransferase [odds ratio (OR), 6.21; 95% confidence interval (CI), 2.48-15.54; P<0.0001], lower albumin (OR, 0.86; 95% CI, 0.78-0.95; P=0.002), platelet count (OR, 0.99; 95% CI, 0.98-0.99; P=0.013), and age (OR, 1.05; 95% CI, 1.01-1.09; P=0.024) as independent predictors of significant fibrosis.

Conclusions: A small but significant minority of HBV patients with low viremia harbor significant fibrosis, although its rate is not different in those with viremia above or below 2000 IU/mL. Our findings may guide in decisions regarding liver biopsy and treatment in this category of patients.
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http://dx.doi.org/10.1097/MCG.0b013e3182a9a2e1DOI Listing
July 2014

In vivo bone regeneration using tubular perfusion system bioreactor cultured nanofibrous scaffolds.

Tissue Eng Part A 2014 Jan 31;20(1-2):139-46. Epub 2013 Aug 31.

1 Fischell Department of Bioengineering, University of Maryland , College Park, Maryland.

The use of bioreactors for the in vitro culture of constructs for bone tissue engineering has become prevalent as these systems may improve the growth and differentiation of a cultured cell population. Here we utilize a tubular perfusion system (TPS) bioreactor for the in vitro culture of human mesenchymal stem cells (hMSCs) and implant the cultured constructs into rat femoral condyle defects. Using nanofibrous electrospun poly(lactic-co-glycolic acid)/poly(ε-caprolactone) scaffolds, hMSCs were cultured for 10 days in vitro in the TPS bioreactor with cellular and acellular scaffolds cultured statically for 10 days as a control. After 3 and 6 weeks of in vivo culture, explants were removed and subjected to histomorphometric analysis. Results indicated more rapid bone regeneration in defects implanted with bioreactor cultured scaffolds with a new bone area of 1.23 ± 0.35 mm(2) at 21 days compared to 0.99 ± 0.43 mm(2) and 0.50 ± 0.29 mm(2) in defects implanted with statically cultured scaffolds and acellular scaffolds, respectively. At the 21 day timepoint, statistical differences (p<0.05) were only observed between defects implanted with cell containing scaffolds and the acellular control. After 42 days, however, defects implanted with TPS cultured scaffolds had the greatest new bone area with 1.72 ± 0.40 mm(2). Defects implanted with statically cultured and acellular scaffolds had a new bone area of 1.26 ± 0.43 mm(2) and 1.19 ± 0.33 mm(2), respectively. The increase in bone growth observed in defects implanted with TPS cultured scaffolds was statistically significant (p<0.05) when compared to both the static and acellular groups at this timepoint. This study demonstrates the efficacy of the TPS bioreactor to improve bone tissue regeneration and highlights the benefits of utilizing perfusion bioreactor systems to culture MSCs for bone tissue engineering.
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http://dx.doi.org/10.1089/ten.TEA.2013.0168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875202PMC
January 2014

Accuracy of international guidelines for identifying significant fibrosis in hepatitis B e antigen--negative patients with chronic hepatitis.

Clin Gastroenterol Hepatol 2013 Nov 28;11(11):1493-1499.e2. Epub 2013 Jun 28.

Department of Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia; Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address:

Background & Aims: Differing threshold levels of hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) are recommended by international guidelines for commencement of antiviral therapy. These guidelines advocate therapy for patients with significant fibrosis (METAVIR score ≥F2); we assessed the accuracy of these guideline-defined thresholds in identifying patients with ≥F2 fibrosis.

Methods: We applied the European (European Association for the Study of the Liver [EASL] 2012), Asian-Pacific (Asian-Pacific Association for the Study of the Liver [APASL] 2012), American (American Association for the Study of Liver Diseases [AASLD] 2009), and United States Panel Algorithm (USPA 2008) criteria to 366 consecutive hepatitis B e antigen-negative patients with liver biopsy samples: EASL, ALT >laboratory-defined upper limit of normal (ULN) and HBV DNA ≥2000 IU/mL (n = 171); APASL, ALT >2-fold laboratory-defined ULN and HBV DNA ≥2000 IU/mL (n = 87); AASLD, ALT >2-fold the updated ULN (0.5-fold ULN [corresponding to ≤19 U/L] for women and 0.75-fold the ULN [corresponding to ≤30 U/L] for men) and HBV DNA ≥20,000 IU/mL (n = 53); and USPA, ALT >updated ULN (>0.5-fold ULN for women and >0.75-fold ULN for men) and HBV DNA ≥2000 IU/mL (n = 173).

Results: Overall, 113 patients (30.9%) had ≥F2 fibrosis, which was more frequent among patients who fulfilled any guideline criteria (45.7% vs 17.9% for those who did not fulfill any criteria, P < .0001). In applying the EASL, AASLD, APASL, and USPA criteria, sensitivity and specificity values for detection of ≥F2 fibrosis were 45.6%, 58.5%, 56.3%, and 45.7% (P = .145) and 82.1%, 73.8%, 77.1%, and 82.4% (P = .366), respectively. The EASL criteria (area under the receiver operating characteristic [AUROC] curve, 0.66; 95% confidence interval [CI], 0.61-0.71) and USPA criteria (AUROC, 0.66; 95% CI, 0.58-0.73) performed better than APASL (AUROC, 0.64; 95% CI, 0.59-0.69; P = .421) and significantly better than the AASLD criteria (AUROC, 0.59; 95% CI, 0.54-0.64; P = .013).

Conclusions: In hepatitis B e antigen-negative patients with chronic hepatitis, the EASL, AASLD, APASL, and USPA criteria identify patients with ≥F2 fibrosis with low levels of accuracy. However, the EASL and USPA criteria are the most accurate for identification of these patients.
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http://dx.doi.org/10.1016/j.cgh.2013.05.038DOI Listing
November 2013