Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT.

Patients with hypomorphic mutations in the RAG1 or RAG2 gene present with either Omenn syndrome or atypical combined immunodeficiency with a wide phenotypic range. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but data are scarce. We report on a worldwide cohort of 60 patients with hypomorphic RAG variants who underwent HSCT, 78% of whom experienced infections (29% active at HSCT), 72% had autoimmunity, and 18% had granulomas pretransplant. These complications are frequently associated with organ damage. Eight individuals (13%) were diagnosed by newborn screening or family history. HSCT was performed at a median of 3.4 years (range 0.3-42.9 years) from matched unrelated donors, matched sibling or matched family donors, or mismatched donors in 48%, 22%, and 30% of the patients, respectively. Grafts were T-cell depleted in 15 cases (25%). Overall survival at 1 and 4 years was 77.5% and 67.5% (median follow-up of 39 months). Infection was the main cause of death. In univariable analysis, active infection, organ damage pre-HSCT, T-cell depletion of the graft, and transplant from a mismatched family donor were predictive of worse outcome, whereas organ damage and T-cell depletion remained significant in multivariable analysis (hazard ratio [HR] = 6.01, HR = 8.46, respectively). All patients diagnosed by newborn screening or family history survived. Cumulative incidences of acute and chronic graft-versus-host disease were 35% and 22%, respectively. Cumulative incidences of new-onset autoimmunity was 15%. Immune reconstitution, particularly recovery of naïve CD4+ T cells, was faster and more robust in patients transplanted before 3.5 years of age, and without organ damage. These findings support the indication for early transplantation.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Development of a new lingual range-of-motion assessment scale: normative data in surgically treated oral cancer patients.

Surgical resection in oral cancer patients can result in altered speech, swallowing, and patient perception of quality of life (QOL). Oral surgery can result in reduced lingual range of motion (ROM). However, few studies have quantified the degree of lingual restriction after surgery. This pilot study describes a new measurement system to define tongue ROM in surgically treated tongue cancer patients. This measurement system was validated by comparing results in these treated surgical patients versus healthy individuals. This scale was further validated by correlating ROM with performance status, oral outcomes, and patient-rated QOL. Thirty-six patients who underwent oral tongue surgery and 31 healthy individuals were included. Tongue ROM was assessed using a novel ROM assessment system. This novel system was examined in these patients versus healthy subjects. This measurement tool was further validated by correlating tongue ROM in treated patients with performance status, oral outcomes, and patient-rated QOL. Tongue ROM was found to be significantly lower in the surgically treated patients than in the healthy individuals (p = 0.0001). Tongue ROM correlated with performance status, oral outcomes, and all QOL measures. This new tongue ROM measurement system defined tongue deficits in surgically treated oral cancer patients. This tool was validated by comparing results to those in healthy individuals, as well as by correlating tongue ROM to performance status, oral outcomes, and QOL. This measurement tool can be used to define baseline and postsurgery tongue ROM in oral cancer patients, as well as track change over time with recovery and therapy. Future studies should examine use of this measurement tool with other populations demonstrating tongue deficits.

Newborn screening for severe combined immunodeficiency: an opportunity for intervention.

Severe combined immunodeficiency (SCID) is a potentially fatal disorder characterized by defective T- and B-lymphocyte function. We describe a 34-week female twin who had developed feeding intolerance, perioral cyanosis, abdominal distension and neutropenia at 1 month of age. Despite several evaluations including an 'inconclusive' newborn screening result for SCID, the presence of profound lymphopenia was unappreciated. Eventually a diagnosis of SCID in association with adenosine deaminase deficiency was made. This case serves to emphasize the importance of newborn screening for SCID in the context of careful evaluation of clinical and laboratory findings that may be overlooked and result in a delay in the diagnosis of a potentially life-threatening condition.

Quality of life after management of advanced osteoradionecrosis of the mandible.

Osteoradionecrosis (ORN) of the mandible is a severe complication of radiation therapy for head and neck cancer. In this case series, the authors analyzed their treatment and quality of life outcomes over the past 6 years. A retrospective chart review of 42 patients treated surgically for advanced ORN was conducted. A telephone survey was conducted and quality of life (QOL) questionnaires were completed in a subset of patients. 30 patients responded to the telephone survey assessing QOL for speech, swallowing and overall functioning correlated with oral nutrition and performance status. Surgery for ORN can result in an improved QOL. Functional outcomes of oral intake, speech intelligibility, and eating in public correlated with patient rated QOL measures. A lack of improvement in QOL, despite the restoration of an intact mandible, relates to the persistent effects of chemoradiotherapy.

Scapular free flap harvest site: recognising the spectrum of radiographic post-operative appearance.

OBJECTIVE: Scapular free flap harvesting for oral cavity cancer reconstruction is an increasingly used and versatile option. We aim to describe the appearance of the scapula harvest site on chest radiograph and CT. METHODS: We retrospectively reviewed a surgical database of 82 patients who underwent scapular osteocutaneous flap harvesting for oral cavity cancer reconstruction and had imaging performed at our institution. We searched the picture archiving and communications system for all associated imaging. RESULTS: Characteristic radiographic appearance in the immediate post-operative period as well as in the remote post-operative period is described, including an upside-down V-shaped paraglenoid notch, rectangular (or triangular) lateral border defects and a sharply pointed inferior scapular body. Additionally, common CT appearances are discussed, including an abrupt gleno-scapular interval, an absent axillary rim bulge and a Z-shaped scapula. CONCLUSION: The altered appearance of the scapular defect following surgical harvest is easily recognised. Although the description of this defect may not alter management and may reasonably be omitted, a radiologist's comfort with these appearances may potentially enhance the understanding of patient management and recognition of superimposed complications, such as infection. ADVANCES IN KNOWLEDGE: Scapular osteocutaneous free flap reconstruction is an increasingly used technique after oral cavity surgery. Very few radiologists reported in our review the surgical scapular defects, and there is apparent ignorance of their appearance. We described characteristic radiographic and CT signs of scapular free flap harvesting to increase radiologists' familiarity with these defects, which may provide clinical information and possibly contribute to detection of complications.

Second malignancies after autologous hematopoietic cell transplantation in children.

Childhood autologous hematopoietic cell transplant (auto-HCT) survivors can be at risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1487 pediatric auto-HCT recipients to investigate the incidence and risk factors for SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma (18%), central nervous system tumors (14%) and Wilms tumor (2%). Median follow-up was 8 years (range, <1-21 years). SMNs were reported in 35 patients (AML/myelodysplastic syndrome (MDS)=13, solid cancers=20, subtype missing=2). The overall cumulative incidence of SMNs at 10 years from auto-HCT was 2.60% (AML/MDS=1.06%, solid tumors=1.30%). We found no association between SMNs risk and age, gender, diagnosis, disease status, time since diagnosis or use of TBI or etoposide as part of conditioning. OS at 5-years from diagnosis of SMNs was 33% (95% confidence interval (CI), 16-52%). When compared with age- and gender-matched general population, auto-HCT recipients had 24 times higher risks of developing SMNs (95% CI, 16.0-33.0). Notable SMN sites included bone (N=5 SMNs, observed (O)/expected (E)=81), thyroid (N=5, O/E=53), breast (N=2, O/E=93), soft tissue (N=2, O/E=34), AML (N=6, O/E=266) and MDS (N=7, O/E=6603). Risks of SMNs increased with longer follow-up from auto-HCT. Pediatric auto-HCT recipients are at considerably increased risk for SMNs and need life-long surveillance for SMNs.

Sinus lift approach for the retrieval of root fragments from the maxillary sinus.

A new application of a well-known technique; lateral wall sinus approach, to remove a root fragment from the maxillary sinus with minimal damage to the epithelial lining and anterior face of maxilla is described. The technique presented in this article helps eliminate some of the complications associated with Caldwell Luc procedure while preserving the epithelial lining of the maxillary sinus and bony face of maxilla.

Prosthodontic guidelines for surgical reconstruction of the maxilla: a classification system of defects.

Surgical reconstruction of maxillectomy defects has been described as an alternative to prosthetic rehabilitation to close the oral cavity. Advancements in microvascular surgical techniques require comprehensive treatment planning guidelines for functional rehabilitation. This retrospective study evaluated acquired maxillectomy defects after surgical reconstruction and/or prosthodontic rehabilitation in an attempt to establish surgical and prosthodontic guidelines that could be organized into a classification system. Forty-seven consecutive patient treatments of palatomaxillary reconstruction at a single facility, The Mount Sinai Medical Center (New York, N.Y.), were reviewed. All patients were rehabilitated with a tissue-borne obturator, a local advancement flap, a fasciocutaneous free flap, or a vascularized bone-containing free flap. Palatomaxillary defects were divided into 3 major classes and 2 subclasses. The aim of this defect-oriented classification system was to organize and define the complex nature of the restorative decision-making process for the maxillectomy patient.

Iliac crest internal oblique osteomusculocutaneous free flap reconstruction of the postablative palatomaxillary defect.

BACKGROUND: Traditionally, restoration of extensive palatomaxillary defects have been achieved by prosthetic restoration, often with suboptimal functional results. More recently, vascularized bone-containing free flaps have been used for this purpose. OBJECTIVE: To describe 6 patients who underwent palatomaxillary reconstruction using the composite iliac crest-internal oblique osteomusculocutaneous free flap. METHODS: Six cases of iliac crest osteomusculocutaneous free flap reconstruction of extensive postablative palatomaxillary defects were retrospectively reviewed with clinical follow-up. We reviewed these cases for pathologic findings, defect size, dental restoration, oral rehabilitation, and speech. RESULTS: Pathologic findings included squamous cell carcinoma (n = 4), osteogenic sarcoma (n = 1), and sinonasal hemangiopericytoma (n = 1). Mean follow-up was 14.5 months (range, 10-25 months). Four patients underwent resection and reconstruction primarily and 2 underwent reconstruction secondarily. Two patients required reconstruction of a cutaneous defect using the iliac skin paddle. The hard palate and lateral nasal wall were reconstructed in all 6 patients, and the orbital rim and zygomatic body were reconstructed in 4. One patient underwent reconstruction with an orbital prosthesis supported by osseointegrated implants. There was 1 donor site complication and 1 recipient site infection, which was treated successfully with oral antibiotics. Four patients were rehabilitated with osseointegrated implants, and all 6 patients maintain an unrestricted oral diet. All 6 patients have normal speech without velopharyngeal or oronasal insufficiency. CONCLUSION: For extensive palatomaxillary defects, the iliac crest-internal oblique osteomusculocutaneous free flap offers a reliable method of primary reconstruction, allowing for complete orodental rehabilitation without the use of a prosthetic obturator.

Acellular dermis for facial soft tissue augmentation: preliminary report.

OBJECTIVE: To evaluate the efficacy of acellular dermis as a viable alternative for soft tissue augmentation in facial reconstruction. DESIGN: A prospective, nonrandomized observational study consisting of 10 patients who underwent soft tissue augmentation with acellular dermis. SETTING: A tertiary care university medical center in an urban setting. PATIENTS: Ten patients who had undergone soft tissue augmentation using acellular dermis participated in this study. Postimplantation follow-up was 17 to 36 months. INTERVENTION: The amount and location for placement of the acellular dermis was left to the discretion of the surgeon. All implants were placed in the subdermal tissues. MAIN OUTCOME MEASURES: The adequacy of acellular dermis for soft tissue augmentation was assessed by subjective evaluation of implant volume persistence, postoperative complications, and the restoration of normal contour. RESULTS: Of 10 patients who underwent implantation, 9 had no complications and 1 had a recurrent sterile abscess or mucocele at the implantation site. A 22-month postimplantation tissue sampling of acellular dermis in a patient with recurrent tumor revealed approximately 80% to 85% volume persistence. CONCLUSION: Preliminary experience with acellular dermis indicates that it shows promise in soft tissue augmentation.

The mandibular symphysis as a donor site in maxillofacial bone grafting: a quantitative anatomic study.

PURPOSE: The goal of this study was to quantify the amount of bone graft material present in the mandibular symphysis as well as to determine the maximal size of the corticocancellous bone block that can be harvested while avoiding mental nerve injury, tooth injury, and simultaneously preserving the preoperative facial contour. MATERIALS AND METHODS: Sixteen fixed dentate cadaver mandibles were studied. Osteotomies were performed in a monocortical fashion, 5 mm anterior to the mental foramen, cephalad to the inferior border of the mandible, caudal to the expected position of the apices of the anterior teeth, and at the midline. The size of the corticocancellous block was then measured. Bone volume, using 2 techniques, was measured by displacement volumetry. RESULTS: The average volumes obtained were 4.84 mL and 4.71 mL (range, 3.25 to 6.50 mL), respectively, for the 2 techniques of volumetry. The average block size was 20.9 x 9.9 x 6.9 mm; the smallest block was 21.0 x 6.5 x 6.0 mm, and the largest was 25.0 x 13.0 x 9.0 mm. CONCLUSION: Based on the results of this study, it is apparent that the mandibular symphysis can be reliably selected as the harvest site in a variety of oral and maxillofacial reconstructive procedures.

Reconstruction of the pediatric maxilla and mandible.

BACKGROUND: The creation of osseous defects in the upper and lower jaws in children is an uncommon occurrence. It is therefore likely that a head and neck reconstructive surgeon will accumulate only limited experience in restoring such defects. We have reviewed 7 pediatric bone-containing microvascular free flap reconstructions in 6 patients for reconstruction of the upper or lower jaws. Three patients were available for long-term follow-up to evaluate the effect of osseous free flap reconstruction on function and growth and development of the donor site. DESIGN: Retrospective review. SETTING: Academic tertiary referral center for otolaryngology. PATIENTS AND METHODS: Six pediatric patients ranging in age from 8 to 16 years underwent 2 fibular, 4 scapular, and 1 iliac free flap procedure for restoration of 2 maxillary and 5 mandibular defects from 1992 to 1997. Three of the 6 patients were available for long-term follow-up to assess the postoperative donor site function in an effort to determine the effect of this surgery on long-term donor site morbidity and development. RESULTS: Two patients were lost to follow-up, and 1 died secondary to complications related to distant metastatic disease. Three of 6 patients were observed for 2 years 6 months, 4 years, and 4 years 2 months, respectively. Two of the 3 patients who were observed long term have undergone full dental rehabilitation and currently maintain a regular diet and deny pain with mastication or deglutition. One patient did not require dental rehabilitation. All 3 patients demonstrate gross facial symmetry and normal dental occlusion. Assessment of the fibular donor site demonstrated normal limb length and circumference. The patients denied pain or restriction to recreational activity. Scapular donor sites demonstrated normal range of motion, strength, and shoulder stability. CONCLUSIONS: Free flap reconstruction of the pediatric maxilla and mandible requires harvesting bone from actively growing donor sites. We have found no evidence of functional deficit after bone harvest from the fibular or scapular donor sites. Patients demonstrate normal growth at the donor sites, and symmetry of the mandible and maxilla is preserved.

Maxillofacial pathology and management of Pierre Robin sequence.

Pierre Robin sequence affects 1:8500 newborns and is characterized by cleft palate, micrognathia, and airway obstruction. Evolution in the understanding of the causes and pathogenesis of this condition is reviewed. Clinical findings and treatment options are also addressed. An overview of syndromes commonly associated with Pierre Robin sequence is provided.

Complications of microvascular head and neck surgery in the elderly.

OBJECTIVES: To evaluate the complications of head and neck reconstruction using microvascular free tissue transfers (MFTTs) performed in an elderly population and to determine whether these complications are more common than in a younger population. SETTING: Tertiary referral center. PATIENTS AND DESIGN: Retrospective, consecutive chart review of patients older than 70 years who underwent MFTT in the past 5 years (group 1). The complications in this population were compared with those in a second group (group 2) of consecutive patients younger than 70 years who were matched according to the site of the primary tumor. MAIN OUTCOME MEASURES: Surgical and medical complications. RESULTS: The median age for group 1 was 74 years and for group 2, 55 years. The overall complication rate for group 1 was 48%, compared with 57% for group 2. In group 1, surgical morbidity was less common and medical morbidity was more common than in group 2. Mortality rate was 6% for group 1 and 0% for group 2. The types of complications were similar for both groups. There was no difference in complication rates when complications were classified by site of the defect, patient status determined by American Society of Anesthesiologists classification, or use of preoperative radiation. The overall success rate of MFTT was 100% for group 1 and 94% for group 2. CONCLUSIONS: Microvascular free tissue transfers for head and neck reconstruction can be safely performed in the elderly. An age older than 70 years does not increase the rate of surgical complications following head and neck reconstruction with MFTT. Medical complications, however, are more common and are equally divided between bronchopulmonary and cardiovascular effects.

Oromandibular reconstruction using microvascular composite flaps: report of 210 cases.

OBJECTIVE: To review the experience of 1 microvascular surgeon during an 11-year period in performing 210 vascularized bone-containing free flaps for oromandibular reconstruction. DESIGN: Retrospective medical records review of patients who underwent primary and secondary oromandibular reconstruction with the use of vascularized bone free flaps. SETTING: Academic medical center. PATIENTS: A total of 201 patients underwent 210 composite free-flap reconstructions of the mandible for various disorders and with a range of bony and soft tissue defects. INTERVENTION: All patients underwent the microvascular transfer of vascularized bone flaps from the ilium, fibula, or scapula. In selected cases, 2 simultaneous free flaps were transferred to achieve an optimal bone and soft tissue reconstruction. Endosteal dental implants were used in 81 patients, with a total of 360 fixtures placed during these 11 years. MAIN OUTCOME MEASURES: The success of microvascular free tissue transfer, dental implant extrusion, and short- and long-term complications at the recipient and donor sites. RESULTS: Of the 210 mandibular reconstructions that were performed, 202 were successful in reestablishing mandibular continuity. Reexploration for vascular-related complications was done in 16 patients, 8 of whom were successfully treated, yielding an overall success rate of 96%. The overall success rate for endosteal dental implants was 92%. The implant success rate was 86% when the bone in which the fixtures were placed was irradiated postoperatively. The success rate was 64% in the 14 fixtures that were placed into previously irradiated bone. CONCLUSIONS: The success of the use of vascularized bone free flaps in restoring continuity to the mandible is clearly demonstrated in this series. There was an acceptable incidence of donor- and recipient-site complications that resulted in minimal long-term morbidity. The careful selection of a donor site(s) for oromandibular reconstruction allows for an optimal restoration of bony and soft tissue defects. Dental implants can be safely used in oromandibular reconstruction with a high level of success. Placing these implants during the initial surgery shortens the duration for achieving dental rehabilitation and enhances the success of the implants when postoperative radiotherapy is administered.

Reconstruction of massive defects in the head and neck: the role of simultaneous distant and regional flaps.

BACKGROUND: Massive defects resulting from excision of advanced head and neck tumors may not be amenable to reconstruction using a single technique of tissue transfer. Sixteen patients undergoing reconstruction using simultaneous free flaps and pedicled regional flaps are presented. METHODS: Regional flaps included the pectoralis major, deltopectoral, cervical visor, paramedian forehead, cervicofacial, and nape of neck flaps. Microvascular tissue transfers included the radial forearm, iliac crest, parascapular/latissimus dorsi, rectus abdominis, fibula, and lateral thigh free flaps. RESULTS: Most defects involved both aerodigestive mucosa and external cutaneous skin. Mucosal reconstruction was carried out using the soft-tissue component of the free flaps, whereas vascularized bone was used for mandibular reconstruction. Regional flaps were used to reconstruct skin of the face and neck. CONCLUSIONS: When planned and applied in a stepwise fashion, simultaneous free flaps and regional flaps are complimentary for the reconstruction of complex wounds in the head and neck.

Regional/local anesthesia: a safe and reasonable choice for patients undergoing carotid endarterectomy.

PURPOSE: The study compares the outcome of carotid endarterectomy in the community hospital setting using regional versus general anesthesia. METHODS: Two hundred thirty-six consecutive operations performed on 200 patients (99 operations using superficial and deep cervical block with local supplementation, and 137 procedures using general anesthesia) during a three-year period were analyzed retrospectively. Noncontinuous data were analyzed using Pearson chi-square, continuous data using Student's t-test. RESULTS: Demographic data and risk factors were similar for both groups. However, patients in the regional anesthesia group had a higher incidence of contralateral stroke and a lower incidence of peripheral vascular disease than patients in the general anesthesia group. Shunts were used less frequently for the regional anesthesia group. The neurologic complication rate was 2.2% for the general anesthesia group and 2.0% for the regional anesthesia group. The single death (fatal stroke) occurred in the general anesthesia group. Four of five major cardiopulmonary complications occurred in the general anesthesia group. CONCLUSIONS: Carotid endarterectomy can be performed with an acceptable neurologic complication rate under either type of anesthesia. Use of regional anesthesia decreases intraoperative shunting and may decrease the rate of cardiopulmonary complications.