Treatment of Hypercalcemic Hyperparathyroidism After Kidney Transplantation Is Associated With Improved Allograft Survival.

BACKGROUND: Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival. MATERIALS AND METHODS: We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups. RESULTS: Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure. CONCLUSIONS: This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.

Pain in Trauma Patients: Measurement and Predisposing Factors.

INTRODUCTION: Acute pain is common after injury. This study intended to evaluate the feasibility of quantifying pain experience over an entire admission using "area under the pain curve" and to identify factors associated with increased pain. METHODS: This retrospective single-center study included all trauma patients admitted from 2013 to 2020. Maximum pain scores were extracted for each day. Pain was defined as area under the curve (AUC) of maximum pain scores/day plotted against time. Injury patterns were analyzed by dichotomizing Abbreviated Injury Scale (AIS) scores (AIS < 3 versus AIS ≥ 3) for each body region. Urinary drug screen results were collected from admission data. A general linear model was used to determine which injury patterns, mechanisms, and age groups were predictive of increased AUC in all patients together and separate by operative and nonoperative groups. RESULTS: We identified 21,640 patients, of which 70% were male and 83% had suffered blunt injury. Overall injury severity was associated with increased pain experience. Serious head injury, younger age, and older age (compared to 45-49 y) were associated with decreased pain. Spinal injuries, thoraco-abdominal injuries, and combined thoracic and lower extremity injuries were predictive of increased pain. Compared to patients with no positive test for illicit substances or documentation of prehospital narcotic medications, the pain experience was greater for both, those who had been administered a narcotic in the prehospital setting and those who tested positive for illicit substances. CONCLUSIONS: This study extends the concept of total pain experience using AUC methodology. Our results demonstrate associations between increased pain and certain patterns of injury, ages, and presence of drugs on admission. Measuring total pain experience could assist in comparing pain-management strategies. Future research should focus on validating pain experience against quality-of-life measurements.

Getting Your Foot in the Door: Access to Surgical Care for Thyroid Disease.

INTRODUCTION: Access to specialty care can be challenging for patients, often involving multiple evaluations, laboratory tests, and referrals. To better understand the different pathways to specialty care, we examined the outcomes of patients evaluated for surgical thyroid disease at a single tertiary referral clinic. METHODS: We reviewed 691 patients seen in the endocrine surgery clinic for thyroid disease (2018-2021). Patient demographics, referral source, referral reason, and reason for not receiving an operation were collected. The number of days from referral to initial clinic visit and from initial clinic visit to an operation were also collected. The Chi-square test, the independent t-test, the Kruskal-Wallis test, the Dunn-Bonferroni post hoc test, and multiple logistic regression tests were performed using SPSS. RESULTS: The top reasons for referral were thyroid nodules (54.4%), hyperthyroidism (26.5%), and multinodular goiter (10.3%). Specialty clinic referrals came from endocrinologists (56.0%), self-referrals (15.5%), and primary care physicians (PCP; 14.4%). Self-referred patients had a shorter waiting time for an appointment than those referred by endocrinologists and PCPs. [median (IQR) (days) 12 (6-17) versus 16 (9-24) versus 16 (9-25), P < 0.001]. Overall, 450 (72.7%) patients underwent thyroid surgery. For those who underwent thyroidectomy, self-referred patients had a shorter time between initial clinic visit and the operation compared to those referred by endocrinologists and PCPs [median (IQR) (days) 2 (1-19) versus 19 (8-33) versus 16 (1-48), P < 0.001]. Patients referred for hyperthyroidism (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.3-10.5, P = 0.012 were more likely to undergo an operation than those referred for other reasons. CONCLUSIONS: Access to specialty care for thyroid disease is facilitated and optimized when self-referrals are permitted. Reducing or eliminating the requirement for a provider referral may improve patients' access.

Preserving the Pipeline of Surgeon Scientists: The Role of a Structured Research Curriculum.

INTRODUCTION: With shrinking National Institute of Health support, increased clinical demands, and less time for research training during residency, the future of surgeon scientists is in jeopardy. We evaluate the role of a structured research curriculum and its association with resident academic productivity. METHODS: Categorical general surgery residents who matched between 2005 and 2019 at our institution were analyzed (n = 104). An optional structured research curriculum, including a mentor program, grant application support, didactic seminars, and travel funding was implemented in 2016. Academic productivity, including the number of publications and citations, was compared between residents who started in or after 2016 (postimplementation, n = 33) and those before 2016 (preimplementation, n = 71). Descriptive statistics, Mann-Whitney U test, multivariable logistic regression, and inverse probability treatment weighting were performed. RESULTS: The postimplementation group had more female (57.6% versus 31.0%, P = 0.010), and nonwhite (36.4% versus 5.6%, P < 0.001) residents and had more publications and citations at the start of residency (P < 0.001). Postimplementation residents were more likely to choose academic development time (ADT) (66.7% versus 23.9%, P < 0.001) and had higher median (IQR) number of publications (2.0 (1.0-12.5) versus 1.0 (0-5.0), P = 0.028) during residency. After adjusting the number of publications at the start of residency, multivariable logistic regression analysis showed that the postimplementation group was five times more likely to choose ADT (95% CI 1.7-14.7, P = 0.04). Further, inverse probability treatment weighting revealed an increase of 0.34 publications per year after implementing the structured research curriculum among residents who chose ADT (95% CI 0.1-0.9, P = 0.023). CONCLUSIONS: A structured research curriculum was associated with increased academic productivity and surgical resident participation in dedicated ADT. A structured research curriculum is effective and should be integrated into residency training to support the next generation of academic surgeons.

Practical Approaches to Advancing Health Equity in Radiology, From the AJR Special Series on DEI.

Despite significant advances in health care, many patients from medically under-served populations are impacted by existing health care disparities. Radiologists are uniquely positioned to decrease health disparities and advance health equity efforts in their practices. However, literature on practical tools for advancing radiology health equity efforts applicable to a wide variety of patient populations and care settings is lacking. Therefore, this article seeks to equip radiologists with an evidence-based and practical knowledge tool kit of health equity strategies, presented in terms of four pillars of research, clinical care, education, and innovation. For each pillar, equity efforts across diverse patient populations and radiology practice settings are examined through the lens of existing barriers, current best practices, and future directions, incorporating practical examples relevant to a spectrum of patient populations. Health equity efforts provide an opportune window to transform radiology through personalized care delivery that is responsive to diverse patient needs. Guided by compassion and empathy as core principles of health equity, the four pillars provide a helpful framework to advance health equity efforts as a step toward social justice in health.

Social Determinants of Health in Imaging-based Cancer Screening: A Case-based Primer with Strategies for Care Improvement.

Health disparities, preventable differences in the burden of disease and disease outcomes often experienced by socially disadvantaged populations, can be found in nearly all areas of radiology, including emergency radiology, neuroradiology, nuclear medicine, image-guided interventions, and imaging-based cancer screening. Disparities in imaging-based cancer screening are especially noteworthy given the far-reaching population health impact. The social determinants of health (SDoH) play an important role in disparities in cancer screening and outcomes. Through improved understanding of how SDoH can drive differences in health outcomes in radiology, radiologists can effectively provide patient-centered, high-quality, and equitable care. Radiologists and radiology practices can become active partners in efforts to assist patients along their imaging journey and overcome existing barriers to equitable cancer screening care for traditionally marginalized populations. As radiology exists at the intersection of diagnostic imaging, image-guided diagnostic intervention, and image-guided treatment, radiologists are uniquely positioned to design these strategies. Cost-effective and socially conscious strategies that address barriers to equitable care can improve both public health and equitable health outcomes. Potential strategies include championing supportive health policy, reducing out-of-pocket costs, increasing price transparency, improving education and outreach efforts, ensuring that appropriate language translation services are available, providing individualized assistance with appointment scheduling, and offering transportation assistance and childcare. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Over-transfusion with blood for suspected hemorrhagic shock is not associated with worse clinical outcomes.

BACKGROUND: We evaluated patient outcomes after early, small volume red blood cell (RBC) transfusion in the setting of presumed hemorrhagic shock. We hypothesized that transfusion with even small amounts of blood would be associated with more complications. STUDY DESIGN AND METHODS: Retrospective review of trauma patients admitted to a Level 1 trauma center between 2016-2021. Patients predicted to require massive transfusion who survived ≥72 h were categorized according to units of RBCs transfused in the first 24 h. A Cox regression model stratified by dichotomized ISS and adjusted for SBP <90 mm Hg and pulse >120 bpm on arrival was used to estimate hazard ratios (HRs) for outcomes of interest. RESULTS: A total of 3121 (24%) received RBC transfusion within the first 24 h. Massive transfusion protocol (MTP) was activated in 38% (1188/3121): 17% received no RBCs, 27.4% 1-3 units, 32.4% 4-9 units, and 22.7% ≥10 units. Mean ISS increased with each category of RBC transfusion. There was no difference in the risk of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), infection, cardiac arrest, venous thromboembolism or stroke for patients receiving 1-3 units compared to the non-transfused group or 4-9 units group (p > 0.05). Compared to those receiving ≥10 units, the 1-3 units group had a significantly lower risk of AKI, ARDS, and cardiac arrest. DISCUSSION: Early empiric RBC transfusion for presumed hemorrhagic shock may subject patients to potential over-transfusion and end-organ damage. Among patients meeting clinical triggers for MTP, 1-3 units of allogeneic RBCs is not associated with worse outcomes.

Evaluation of Injury Recidivism Using the Electronic Medical Record.

BACKGROUND: Traumatic injuries remain one of the leading causes of death in the United States. Patients who survive traumatic injuries but return to the emergency department with repeat injuries are said to suffer from injury recidivism. Numerous studies have described trends in injury recidivism using trauma registry and survey data. To our knowledge, no prior study has leveraged electronic medical record (EMR) data to characterize injury recidivism. The EMR is potentially more comprehensive as it contains details of patients who visited the emergency department after injury but did not meet the criteria for inclusion in the trauma registry. Such injuries could be predictive of future recidivism. We therefore aimed to describe patterns of injury recidivism seen at a Level 1 trauma center using the EMR. METHODS: A retrospective review was conducted of all injury-related encounters between January 2016 and December 2019. Manual review was conducted of all recidivistic encounters with < 11 months between encounters to ensure the recidivistic encounter was not a sequela of the index visit. A general estimating equation logistic regression adjusted for age, race, sex, and insurance payor, estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between injury mechanism and odds of recidivistic encounter. RESULTS: A total of 20,566 index encounters was included during the study period. Of the 20,566 encounters, 7.6% (n = 1570) had a recidivistic encounter during the study period, half of which (n = 781) occurred within the first year of the index encounter. An over two-fold increased odds of recidivism was observed for blunt assault encounters (OR 2.53, 95% CI 2.03-3.15) and unintentional falls (OR 2.10, 95% CI 1.76-2.52). For both mechanisms, this increase was observed across the three years following the index encounter. CONCLUSIONS: Our study found that patients with assault injuries have the highest odds of injury recidivism and assault-related recidivistic encounters. These results demonstrate the feasibility and utility of incorporating EMR data, and suggest that the development of targeted interventions focused on mitigating assault injuries, such as hospital-based violence intervention programs, should be considered in our region.

Central Nervous System Systemic Lupus Erythematosus (CNS-SLE) Vasculitis Mimicking Lewy Body Dementia: A Case Report Emphasizing the Role of Imaging With an Analysis of 33 Comparable Cases From the Scientific Literature.

INTRODUCTION: Neuropsychiatric symptoms occur in 30% to 40% of patients living with systemic lupus erythematosus (SLE). Brain imaging may play a pivotal role in determining the etiology as it did for the case presented here. METHODS: A new case of central nervous system (CNS) SLE is presented along with an analysis of 33 comparable cases from the scientific literature. RESULTS: A 70-year-old female with subacute cutaneous lupus presented to a university-based geropsychiatry program after 1 year of benign visual hallucinations and several months of shuffling gait, recurrent falls, and forgetfulness. These symptoms were highly suggestive of Lewy body dementia; however, the patient's history of basal ganglia infarct, cognitive testing demonstrating inattention and executive dysfunction, and follow-up brain imaging, which did not reveal acute findings, aligned with cerebral pathology previously attributed to vasculitis and supported the diagnosis of subcortical dementia due to SLE-CNS vasculitis. Oral prednisone 20 mg daily resolved her symptoms. Over the next 19 months, her prednisone was tapered completely and her symptoms did not return. A systematic literature search identified 33 comparable cases. CONCLUSION: An analysis of previously published cases suggests that extending the duration of the prednisone taper beyond 1 year may decrease the risk of later occurring neuropsychiatric symptoms in this patient population.

Case 279: Central-Variant Posterior Reversible Encephalopathy Syndrome.

HistoryA 25-year-old woman with recently diagnosed systemic lupus erythematosus and class IV lupus nephritis confirmed with biopsy and treated with mycophenolate mofetil presented with a 2-day history of progressively worsening edema of her face and lower extremities. She had no antecedent infection or vaccination. She was admitted to the hospital and treated with methylprednisolone, furosemide, and C1 esterase inhibitor. On hospital day 2, she experienced a witnessed generalized tonic-clonic seizure. At that time, she became hypoxic and was intubated for airway protection. Her laboratory study results preceding the seizure were remarkable for hyponatremia, with a blood sodium level of 122 mEq/L (122 mmol/L) (normal range, 135-145 mEq/L [134-145 mmol/L]), which was corrected to 137 mEq/L (137 mmol/L) over 48 hours. Same-day cerebrospinal fluid analysis was unremarkable, and unenhanced head CT findings (not shown) were normal, with no evidence of intracranial hemorrhage or edema.Her subsequent hospital course was complicated by renal failure requiring continuous renal replacement therapy, hypertension (systolic blood pressure ranging from 140 to 190 mm Hg), anemia requiring blood transfusions, thrombocytopenia, and pneumonia. She remained intubated with a limited neurologic examination due to sedative medications until hospital day 10. After extubation, she was noted to have a right gaze preference. She was able to speak in short phrases and follow simple commands. Neurologic examination was notable for drowsiness, right gaze deviation, direction-changing torsional nystagmus, horizontal ophthalmoplegia, and generalized symmetric weakness without upper motor neuron signs. The following day (hospital day 11), unenhanced MRI of the brain was performed along with MR angiography of the brain. Biopsy of the temporal artery was normal, without evidence of inflammation.

Case 279.

HistoryA 25-year-old woman with recently diagnosed systemic lupus erythematosus and class IV lupus nephritis confirmed with biopsy and treated with mycophenolate mofetil presented with a 2-day history of progressively worsening edema of her face and lower extremities. She had no antecedent infection or vaccination. She was admitted to the hospital and treated with methylprednisolone, furosemide, and C1 esterase inhibitor. On hospital day 2, she experienced a witnessed generalized tonic-clonic seizure. At that time, she became hypoxic and was intubated for airway protection. Her laboratory study results preceding the seizure were remarkable for hyponatremia, with a blood sodium level of 122 mEq/L (122 mmol/L) (normal range, 135-145 mEq/L [134-145 mmol/L]), which was corrected to 137 mEq/L (137 mmol/L) over 48 hours. Same-day cerebrospinal fluid analysis was unremarkable, and unenhanced head CT findings (not shown) were normal, with no evidence of intracranial hemorrhage or edema.

Impact of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the costs of mitigation.

Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36-3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40-0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions.

Cost-effectiveness of Intraoperative MRI for Treatment of High-Grade Gliomas.

Background Intraoperative MRI has been shown to improve gross-total resection of high-grade glioma. However, to the knowledge of the authors, the cost-effectiveness of intraoperative MRI has not been established. Purpose To construct a clinical decision analysis model for assessing intraoperative MRI in the treatment of high-grade glioma. Materials and Methods An integrated five-state microsimulation model was constructed to follow patients with high-grade glioma. One-hundred-thousand patients treated with intraoperative MRI were compared with 100 000 patients who were treated without intraoperative MRI from initial resection and debulking until death (median age at initial resection, 55 years). After the operation and treatment of complications, patients existed in one of three health states: progression-free survival (PFS), progressive disease, or dead. Patients with recurrence were offered up to two repeated resections. PFS, valuation of health states (utility values), probabilities, and costs were obtained from randomized controlled trials whenever possible. Otherwise, national databases, registries, and nonrandomized trials were used. Uncertainty in model inputs was assessed by using deterministic and probabilistic sensitivity analyses. A health care perspective was used for this analysis. A willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained was used to determine cost efficacy. Results Intraoperative MRI yielded an incremental benefit of 0.18 QALYs (1.34 QALYs with intraoperative MRI vs 1.16 QALYs without) at an incremental cost of $13 447 ($176 460 with intraoperative MRI vs $163 013 without) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio of $76 442 per QALY. Because of parameter distributions, probabilistic sensitivity analysis demonstrated that intraoperative MRI had a 99.5% chance of cost-effectiveness at a willingness-to-pay threshold of $100 000 per QALY. Conclusion Intraoperative MRI is likely to be a cost-effective modality in the treatment of high-grade glioma. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Bettmann in this issue.

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: evidence from health facility data from Benin.

BACKGROUND: Insecticide-based interventions have averted more than 500 million malaria cases since 2000, but insecticide resistance in mosquitoes could bring about a rebound in disease and mortality. This study investigated whether insecticide resistance was associated with increased incidence of clinical malaria. METHODS: In an area of southern Benin with insecticide resistance and high use of insecticide-treated nets (ITNs), malaria morbidity and insecticide resistance were measured simultaneously in 30 clusters (villages or collections of villages) multiple times over the course of 2 years. Insecticide resistance frequencies were measured using the standard World Health Organization bioassay test. Malaria morbidity was measured by cases recorded at health facilities both in the whole population using routinely collected data and in a passively followed cohort of children under 5 years old. RESULTS: There was no evidence that incidence of malaria from routinely collected data was higher in clusters with resistance frequencies above the median, either in children aged under 5 (RR = 1.27 (95% CI 0.81-2.00) p = 0.276) or in individuals aged 5 or over (RR = 1.74 (95% CI 0.91-3.34) p = 0.093). There was also no evidence that incidence was higher in clusters with resistance frequencies above the median in the passively followed cohort (RR = 1.11 (0.52-2.35) p = 0.777). CONCLUSIONS: This study found no association between frequency of resistance and incidence of clinical malaria in an area where ITNs are the principal form of vector control. This may be because, as other studies have shown, ITNs continue to offer some protection from malaria even in the presence of insecticide resistance. Irrespective of resistance, nets provide only partial protection so the development of improved or supplementary vector control tools is required to reduce Africa's unacceptably high malaria burden.

Impact of preoperative endovascular embolization on immediate meningioma resection outcomes.

OBJECTIVE Preoperative embolization of meningiomas can facilitate their resection when they are difficult to remove. The optimal use and timing of such a procedure remains controversial given the risk of embolization-linked morbidity in select clinical settings. In this work, the authors used a large national database to study the impact of immediate preoperative embolization on the immediate outcomes of meningioma resection. METHODS Meningioma patients who had undergone elective resection were identified in the National (Nationwide) Inpatient Sample (NIS) for the period 2002-2014. Patients who had undergone preoperative embolization were propensity score matched to those who had not, adjusting for patient and hospital characteristics. Associations between preoperative embolization and morbidity, mortality, and nonroutine discharge were investigated. RESULTS Overall, 27,008 admissions met the inclusion criteria, and 633 patients (2.34%) had undergone preoperative embolization and 26,375 (97.66%) had not. The embolization group was younger (55.17 vs 57.69 years, p < 0.001) with a lower proportion of females (63.5% vs 69.1%, p = 0.003), higher Charlson Comorbidity Index (p = 0.002), and higher disease severity (p < 0.001). Propensity score matching retained 413 embolization and 413 nonembolization patients. In the matched cohort, preoperative embolization was associated with increased rates of cerebral edema (25.2% vs 17.7%, p = 0.009), posthemorrhagic anemia or transfusion (21.8% vs 13.8%, p = 0.003), and nonroutine discharge (42.8% vs 35.7%, p = 0.039). There was no difference in mortality (≤ 2.4% vs ≤ 2.4%, p = 0.82). Among the embolization patients, the mean interval from embolization to resection was 1.49 days. On multivariate analysis, a longer interval was significantly associated with nonroutine discharge (OR 1.33, p = 0.004) but not with complications or mortality. CONCLUSIONS Relative to meningioma patients who do not undergo preoperative embolization in the same admission, those who do have higher rates of cerebral edema and nonroutine discharge but not higher rates of stroke or death. Thus, meningiomas requiring preoperative embolization represent a distinct clinical entity that requires prolonged, more complex care. Further, among embolization patients, the timing of resection did not affect the risk of in-hospital complications, suggesting that the timing of surgery can be determined according to surgeon discretion.

Predictors of Postoperative Complications of Craniosynostosis Repair in the National Inpatient Sample.

INTRODUCTION: Timing of intervention and complication profiles in surgical repair of craniosynostosis have been widely debated. Early intervention is frequently promoted as a means of decreasing morbidity while maintaining favorable outcomes via minimally invasive techniques such as endoscopic strip craniectomy. Immediate postoperative morbidity due to complications of early vs late intervention remains a key element in comparing timing and technique for craniosynostosis repair. In addition, concurrent fronto-orbital advancement with open cranial vault remodeling may increase the risk of postoperative complications. We present an evaluation of surgical timing and the presence of fronto-orbital advancement as independent predictors of in-hospital complications after craniosynostosis repair. METHODS: Retrospective analysis was performed in the National Inpatient Sample database from 1998 to 2009. Patients younger than 3 years having undergone elective surgical repair for craniosynostosis were identified. Comorbidities, demographics, transfusion status, and syndromic diagnosis were included as covariates. A multivariate regression model was used to characterize the association between age at the time of surgery and in-hospital complications. A subgroup analysis using the variable of concurrent fronto-orbital advancement was restricted to patients 8 to 24 months of age to exclude endoscopic craniosynostosis repair, which is traditionally repaired less than 6 months of age. Multivariate logistic regression was used to assess the impact of concurrent fronto-orbital advancement on postoperative complications. RESULTS: A total of 6010 craniosynostosis surgery cases (42.9%, age 0-7 months; 29.5%, age 8-12 months; and 27.6%, age 13-36 months) were included. Patients in the 7-to 12-month age group were more likely to experience complications when compared with the 0- to 6-month age group (odds ratio [OR],1.32; P < 0.05) and 13-to 36-month age group (OR, 1.32; P = 0.056). Syndromic patients (OR, 1.92; P < 0.001) and patients receiving an intraoperative blood transfusion (OR, 1.60; P < 0.05) demonstrated an increased risk for complications. In the subanalysis of 2936 patients aged 8 to 24 months, 15.1% of patients received frontoorbital advancement, which was associated with a significantly increased risk of complications (OR, 1.43; P < 0.05). CONCLUSIONS: Intermediate age (7-12 months) and concurrent fronto-orbital repair were independent risk factors for immediate postoperative complications. These findings may better inform the decision-making process for craniosynostosis repair in terms of timing and need for concurrent fronto-orbital reconstruction.

Intracranial Hypotension and Hypertension Associated With Reconstructive Cranioplasty After Decompressive Craniectomy: Report of a Lethal Complication With Recommended Strategies for Future Avoidance.

Reconstructive cranioplasty can be associated with many complications and add to the not insignificant potential risks associated with decompressive craniectomy. In the setting of post-traumatic hydrocephalus, treatment with a ventriculoperitoneal (VP) shunt prior to reconstructive cranioplasty likely increases these risks even further. The authors report a case of a 17-year-old male with a history of a severe closed head injury who initially suffered a life-threatening complication associated with intracranial hypotension after cranioplasty only to succumb to malignant intracranial hypertension following a second cranioplasty attempt. To our knowledge, this is the first description of a single patient developing both these disparate complications after reconstructive cranioplasty and emphasizes the likely synergistic hazards involved with decompressive craniectomy in the setting of a VP shunt in particular and the overall myriad potential complications that may be associated with reconstructive cranioplasty in general.

IFN-ß treatment requires B cells for efficacy in neuroautoimmunity.

IFN-ß remains the most widely prescribed treatment for relapsing remitting multiple sclerosis. Despite widespread use of IFN-ß, the therapeutic mechanism is still partially understood. Particularly, the clinical relevance of increased B cell activity during IFN-ß treatment is unclear. In this article, we show that IFN-ß pushes some B cells into a transitional, regulatory population that is a critical mechanism for therapy. IFN-ß treatment increases the absolute number of regulatory CD19(+)CD24(++)CD38(++) transitional B cells in peripheral blood relative to treatment-naive and Copaxone-treated patients. In addition, we found that transitional B cells from both healthy controls and IFN-ß-treated MS patients are potent producers of IL-10, and that the capability of IFN-ß to induce IL-10 is amplified when B cells are stimulated. Similar changes are seen in mice with experimental autoimmune encephalomyelitis. IFN-ß treatment increases transitional and regulatory B cell populations, as well as IL-10 secretion in the spleen. Furthermore, we found that IFN-ß increases autoantibody production, implicating humoral immune activation in B cell regulatory responses. Finally, we demonstrate that IFN-ß therapy requires immune-regulatory B cells by showing that B cell-deficient mice do not benefit clinically or histopathologically from IFN-ß treatment. These results have significant implications for the diagnosis and treatment of relapsing remitting multiple sclerosis.