[3368741]
An initial spontaneous report assessed as non-serious was received on (b)(6) 2009 from an oral surgeon regarding gem-215 concerning a (b)(6) male. On (b)(6) 2010, the following additional details were received in which the report was assessed by luitpold pharmaceuticals inc. As serious. The patient was reported as having no pre-existing medical history with no concomitant medication history. The patient had a dental history of alveolar width insufficiency relative to implant placement. On (b)(6) 2009, the patient underwent a bone graft of the left posterior mandible in which the practitioner employed a mixture of gem-215 (lot # pc0081, exp. Date 04/2010) with allogenic, autologous and cancellous bone (off label method of use). The gem-215 was reported as single use. Intraoperative medications included fentanyl and clindamycin 600 mg. (routes not specified). The patient was prescribed a post operative course of clindamycin and oral vicodin. On (b)(6) 2009, the patient contacted the practitioner to report that the incision site had opened up. An office visit the same day confirmed dehiscence of the surgical incision (medra coded as wound dehiscence). The practitioner reported that the tissue surrounding the surgical site had a hard, fibrotic appearance (medra coded as soft tissue disorder). Treatment included minimal debridement of fibrotic tissue and loose surface bone with instruction to continue soft diet and peridex oral rinse. A follow-up exam on (b)(6) 2009 revealed further dehiscence of the surgical site. Treatment continued with a soft diet and peridex: the antibiotic was changed to flagyl. On (b)(6) 2009, the patient was seen for follow-up; no improvement was noted. Over a period of 6 months, there were spotty 1 cm. Areas of formation of granulation tissue at the surgical site, but the wound never closed (medra codes as impaired healing). No signs of infection were noted during this time. Surgical closure of the wound was scheduled (b)(6) 2009. The oral surgeon removed what was described as bone that failed to integrate and debrided areas of hard fibrotic tissue. The wound has since remained closed without complications. Follow-up received on (b)(6) 2010: luitpold pharmaceuticals, inc. Dental consultant obtained the following update from the initial reporter (oral surgeon) on (b)(4) 2010. According to the oral surgeon, a well-nourished, healthy (b)(6) male with no significant past medical history findings and on no medications presented to his office with alveolar width insufficiency of the left posterior mandible. On (b)(6) 2009 large soft tissue flaps were developed with significant buccal muscle release. Intramarrow penetration of the mandibular crest was performed in order to obtain a bleeding graft site. At the same time a corticocancellous autogenous graft from the left retromolar area was obtained. The autogenous particulate graft was mixed with beta-tcp + rhpdgf-bb (gem 215). An allogenic j-block was then grafted to the deficient mandible and screwed into place. The autogenous bone + beta-tcp + rhpdgf-bb composite graft was then placed around the entire perimeter of the j-block graft, a bio-gide membrane positioned over the grafted site, and the entire area closed primarily without tension by repositioning the full-thickness mucoperiosteal flaps, on (b)(6) 2009 the patient presented with a large wound dehiscence of almost the entire initial incision. A significant portion of the j-block, as well as the particulate graft material, was exposed. According to the oral surgeon, the mucosal wound edges were round and hardened. No erythema or inflammation was present and there were no local or systemic signs of infection. The patient had mild discomfort but did not complain of overt pain. On (b)(6) 2009 the oral surgeon debrided the exposed area, removing all of the corticocancellous + beta tcp + rhpdg-bb composite graft. The j-block was left intact. The oral surgeon then regrafted around the j-block with a composite graft of bio-oss particulate and allogenic cancellous bone. In this second surgery, rhpdg-bb was not used. A bio-gide membrane was placed over the graft material and the surgical site was closed primarily. On (b)(6) 2009 the incision site reopened and remained open for approximately the next 8 months. Following the (b)(6) dehiscence small areas of granulation tissue formed, but according to the oral surgeon did not continue to full soft tissue closure over the exposed site. The oral surgeon stated that the granulation tissue continued to form and then disappear for the next two months, following which no further granulation occurred. During this time the hardening of the wound margins persisted and appeared to spread approximately 1 cm laterally into the surrounding mucosa. No overt evidence of bone or soft tissue necrosis was evident during the entire 8 month duration, nor was there evidence of erythema or frank inflammation. The patient continued to have minimal discomfort. On (b)(6) 2009 the j-block and a small superficial bony sequestrum were removed. No evidence of the previously grafted bio-oss + allogenic cancellous composite graft was present. The area was then closed primarily and has remained closed since. No biopsy of hard or soft tissue was done at any point in time from (b)(6) 2009. According to the oral surgeon, the patient denied any history of taking oral or intravenous bisphosphonates, ruling out the possibility of osteonecrosis of the jaws (onj) secondary to bisphosphonates. The patient also denied any history of radiation treatment to the head and neck areas as well as any self-imposed injury to the surgical site. The oral surgeon presented the facts of this case to a number of clinicians who could offer no explantation of the above findings except for disordered wound healing of unknown origin. Company causality assessment: although soft tissue wound dehiscence is not uncommon, several findings in this case are unusual and include the following: the hardening of mucosal incision/wound edges approximately 5 days following the initial surgery; lack of adequate granulation tissue formation; little to no inflammatory response in spite of an open wound. Although thickened, rolled and indurated wound margins are common in prolonged delayed healing, their presence 5 days post-operatively is highly unusual and suggests aberration in soft tissue wound healing. Assessing and identifying the possible role of graft materials to this patient's unusual healing response is difficult since multiple graft materials were used in this case, i. E. Corticocancellous autogenous bone, allogenic j-block, beta tcp + rhpdgf=bb, bio-oss particulate, allogenic cancellous particulate, all covered with a bio-gide membrane, isolating any one graft type, including rhpdgf-bb, as a possible primary cause of the patient's initial and then persistent healing delay is difficult, if not impossible. What is notable, however, is that rapid and complete wound closure occurred once the j-block was removed, suggesting that the presence of the j-block may have played significant roles in the initial soft tissue dehiscences well as in the persistent delay over an 8 month period of definitive soft tissue healing. It is impossible to speculate whether any of the other graft materials, including rhpdgf-bb, played definitive roles in this patient's prolonged wound healing. That removal of the j-block finally led to rapid wound closure strongly suggests that its presence was in all likelihood a major etiologic factor in this patient's problem.
Patient Sequence No: 1, Text Type: D, B5