Localized application of SAG21k-loaded fibrin hydrogels for targeted modulation of the hedgehog pathway in facial nerve injury.

Given the broad biological effects of the Hedgehog (Hh) pathway, there is potential clinical value in local application of Hh pathway modulators to restrict pathway activation of target tissues and avoid systemic pathway activation. One option to limit Hh pathway activation is using fibrin hydrogels to deliver pathway modulators directly to tissues of interest, bypassing systemic distribution of the drug. In this study, we loaded the potent Hh pathway agonist, SAG21k, into fibrin hydrogels. We describe the binding between fibrin and SAG21k and achieve sustained release of the drug in vitro. SAG21k-loaded fibrin hydrogels exhibit strong biological activity in vitro, using a pathway-specific reporter cell line. To test in vivo activity, we used a mouse model of facial nerve injury. Application of fibrin hydrogels is a common adjunct to surgical nerve repair, and the Hh pathway is known to play an important role in facial nerve injury and regeneration. Local application of the Hh pathway agonist SAG21k using a fibrin hydrogel applied to the site of facial nerve injury successfully activates the Hh pathway in treated nerve tissue. Importantly, this method appears to avoid systemic pathway activation when Hh-responsive organs are analyzed for transcriptional pathway activation. This method of local tissue Hh pathway agonist administration allows for effective pathway targeting surgically accessible tissues and may have translational value in situations where supranormal pathway activation is therapeutic.

Graftless Immediate Dual Implant Anatomic Placement With Immediate Provisional Passive Loading and Definitive Hybrid Crown for the Restoration of Mandibular Molar: A Clinical Report.

Immediate implant placement is well-known science and treatment in implant dentistry. It is a multitasking treatment consisting of surgical, prosthodontic, and periodontal aspects, implemented to obtain long-term clinically esthetic and functioning prosthesis. Immediate placement enables clinicians to reduce the number of surgical steps and shorter treatment duration. It has become a standard surgical protocol in modern implant practice. According to existing literature, dual implant placement can be done to avoid any cantilever effect in a single implant and to distribute masticatory forces. This clinical report describes the extraction of an infected mandibular right first molar, (46, Federation Dentaire Internationale) followed by immediate dual placement of dental implants in the rinsed and cleansed sockets. The tooth was atraumatically extracted from the socket, and the latter was prepared to the required depth, and endosseous implants were placed in both the mesial and distal sockets. This atraumatic graft-free operating technique and immediate placement resulted in the preservation of hard and soft tissues. It also increased the patient's comfort, acceptance, and satisfaction due to immediate loading with a provisional removable prosthesis. This was later replaced with a dual screw-retained hybrid implant crown.

Pathological outcomes and biochemical recurrence-free survival after radical prostatectomy for high-risk prostate cancer in the Indian population.

INTRODUCTION: We analyzed the biochemical recurrence-free survival (BRFS) of patients with high-risk prostate cancer (HRCaP) as per the D'Amico classification undergoing radical prostatectomy (RP) at our center. We aimed to determine whether the number and type of risk factors (cT2c-T3b, prostate-specific antigen >20 ng/ml, Gleason score >7) are associated with biochemical recurrence (BCR) in HRCaP patients undergoing RP in the Indian population. METHODS: Between 2006 and 2017, 192 patients underwent RP (open RP [ORP], laparoscopic RP [LRP], and robotic RP [RRP]) at our center, of which 109 had D'Amico HR disease. Preoperative, postoperative, and pathological outcome data were analyzed for patients with HR disease as per the D'Amico classification. Subgroups were formed to determine whether an increasing number of risk factors (1, 2, or 3) were associated with poorer oncological results and early BCR. The Kaplan-Meier method with log-rank test was used to test the difference in BRFS between the groups. Univariate and multivariate analyses were done to find significant variable against BCR. RESULTS: According to the D'Amico criteria, 109 patients had HR, 63 patients had intermediate-risk, and 19 patients had low-risk disease. These 109 patients with HR disease were analyzed in our study (50 RRP, 33 ORP, and 26 LRP). A total of 59 (54.1%) patients had one HR factor (1HR), 44 (40%) had two HR factors (2HR), and 6 (5.5%) had three HR factors (3HR). The mean follow-up for our patient population was 21.5 ± 19 months (median 18 months; range, 0-108). Overall, the 2-year and 5-year BRFS was 45% and 35%, respectively (mean BRFS 46 ± 6 months). Two-year BRFS was 63%, 23%, and 22%, respectively, for 1HR, 2HR, and 3HR (logrank, P < 0.0001). The prognostic substratification based on the three risk factors was significantly predictive for adverse pathologic features and oncologic outcomes. CONCLUSION: Substratification based on the three well-defined criteria leads to a better identification of the more aggressive cancers and prediction of need for additional treatment modalities. Localized HRCaP includes a heterogeneous population of patients with variable oncological outcomes.

Castleman's Disease: a Suprarenal Surprise!

Castleman's disease is a distinct form of lymph node hyperplasia. It commonly presents as a mediastinal mass and rarely as a solitary retroperitoneal mass. We narrate a case of Castleman's disease presenting as a right suprarenal mass emphasising the usefulness of robot-assisted retroperitoneoscopy in surgical management of retroperitoneal masses in close relation to vital structures.