Discrepancy between global- and disease-specific outcome measures following lumbar spine surgery.

OBJECTIVE: The aim of this study was to assess the correlation between patient-perceived changes in health and commonly utilized patient-reported outcome measures (PROMs) in lumbar spine surgery. METHODS: This was a retrospective review of prospectively collected data on consecutive patients who underwent lumbar microdiscectomy, lumbar decompression, or lumbar fusion at a single academic institution from 2017 to 2023. Correlation between the global rating of change (GRC) questionnaire, a 5-item Likert scale (much better, slightly better, about the same, slightly worse, and much worse), and PROMs (Oswestry Disability Index, visual analog scale for back and leg pain, 12-Item Short Form Health Survey Physical Component Summary and Mental Component Summary, and PROMIS physical function) was assessed using Spearman's rank correlation coefficients. RESULTS: A total of 1871 patients (397 microdiscectomies, 965 decompressions, and 509 fusions) were included. A majority of patients in each group rated their lumbar condition as much better at each postoperative time point compared with preoperatively and reported improved health status at each postoperative time point compared with the previous follow-up visit. Statistically significant but weak to moderate correlations were found between GRC and change in PROM scores from the preoperative time point. Correlation between GRC and change in PROM scores from the prior visit showed some statistically significant correlations, but the strengths ranged from very weak to weak. CONCLUSIONS: A majority of patients undergoing lumbar microdiscectomy, decompression, or fusion endorsed notable improvements in health status in the early postoperative period and continued to improve at late follow-up. However, commonly used PROMs demonstrated very weak to moderate correlations with patient-perceived changes in overall lumbar spine-related health status as determined by GRC. Therefore, currently used PROMs may not be as sensitive at detecting these changes or may not be adequately reflecting changes in health conditions that are meaningful to patients undergoing lumbar spine surgery.

Level-specific comparison of 3D navigated and robotic arm-guided screw placement: an accuracy assessment of 1210 pedicle screws in lumbar surgery.

BACKGROUND CONTEXT: Robotic spine surgery, utilizing 3D imaging and robotic arms, has been shown to improve the accuracy of pedicle screw placement compared to conventional methods, although its superiority remains under debate. There are few studies evaluating the accuracy of 3D navigated versus robotic-guided screw placement across lumbar levels, addressing anatomical challenges to refine surgical strategies and patient safety. PURPOSE: This study aims to investigate the pedicle screw placement accuracy between 3D navigation and robotic arm-guided systems across distinct lumbar levels. STUDY DESIGN: A retrospective review of a prospectively collected registry PATIENT SAMPLE: Patients undergoing fusion surgery with pedicle screw placement in the prone position, using either via 3D image navigation only or robotic arm guidance OUTCOME MEASURE: Radiographical screw accuracy was assessed by the postoperative computed tomography (CT) according to the Gertzbein-Robbins classification, particularly focused on accuracy at different lumbar levels. METHODS: Accuracy of screw placement in the 3D navigation (Nav group) and robotic arm guidance (Robo group) was compared using Chi-squared test/Fisher's exact test with effect size measured by Cramer's V, both overall and at each specific lumbosacral spinal level. RESULTS: A total of 321 patients were included (Nav, 157; Robo, 189) and evaluated 1210 screws (Nav, 651; Robo 559). The Robo group demonstrated significantly higher overall accuracy (98.6 vs. 93.9%; p<.001, V=0.25). This difference of no breach screw rate was signified the most at the L3 level (No breach screw: Robo 91.3 vs. 57.8%, p<.001, V=0.35) followed by L4 (89.6 vs. 64.7%, p<.001, V=0.28), and L5 (92.0 vs. 74.5%, p<.001, V=0.22). However, screw accuracy at S1 was not significant between the groups (81.1 vs. 72.0%, V=0.10). CONCLUSION: This study highlights the enhanced accuracy of robotic arm-guided systems compared to 3D navigation for pedicle screw placement in lumbar fusion surgeries, especially at the L3, L4, and L5 levels. However, at the S1 level, both systems exhibit similar effectiveness, underscoring the importance of understanding each system's specific advantages for optimization of surgical complications.

Practical Answers to Frequently Asked Questions in Anterior Cervical Spine Surgery for Degenerative Conditions.

INTRODUCTION: Surgical counseling enables shared decision making and optimal outcomes by improving patients' understanding about their pathologies, surgical options, and expected outcomes. Here, we aimed to provide practical answers to frequently asked questions (FAQs) from patients undergoing an anterior cervical diskectomy and fusion (ACDF) or cervical disk replacement (CDR) for the treatment of degenerative conditions. METHODS: Patients who underwent primary one-level or two-level ACDF or CDR for the treatment of degenerative conditions with a minimum of 1-year follow-up were included. Data were used to answer 10 FAQs that were generated from author's experience of commonly asked questions in clinic before ACDF or CDR. RESULTS: A total of 395 patients (181 ACDF, 214 CDR) were included. (1, 2, and 3) Will my neck/arm pain and physical function improve? Patients report notable improvement in all patient-reported outcome measures. (4) Is there a chance I will get worse? 13% (ACDF) and 5% (CDR) reported worsening. (5) Will I receive a significant amount of radiation? Patients on average received a 3.7 (ACDF) and 5.5 mGy (CDR) dose during. (6) How long will I stay in the hospital? Most patients get discharged on postoperative day one. (7) What is the likelihood that I will have a complication? 13% (8% minor and 5% major) experienced in-hospital complications (ACDF) and 5% (all minor) did (CDR). (8) Will I need another surgery? 2.2% (ACDF) and 2.3% (CDR) of patients required a revision surgery. (9 & 10) When will I be able to return to work/driving? Most patients return to working (median of 16 [ACDF] and 14 days [CDR]) and driving (median of 16 [ACDF] and 12 days [CDR]). CONCLUSIONS: The answers to the FAQs can assist surgeons in evidence-based patient counseling.

Impact of Preoperative Symptom Duration on Patient-Reported Outcomes Following Cervical Disc Replacement for Cervical Radiculopathy.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To determine the impact of preoperative symptom duration on postoperative functional outcomes following cervical disc replacement (CDR) for radiculopathy. SUMMARY OF BACKGROUND DATA: CDR has emerged as a reliable and efficacious treatment option for degenerative cervical spine pathologies. The relationship between preoperative symptom duration and outcomes following CDR is not well established. METHODS: Patients with radiculopathy without myelopathy who underwent primary 1- or 2-level CDRs were included and divided into shorter (<6 mo) and prolonged (≥6 mo) cohorts based on preoperative symptom duration. Patient-reported outcome measures (PROMs) included Neck Disability Index (NDI), Visual Analog Scale (VAS) Neck and Arm. Change in PROM scores and minimal clinically important difference (MCID) rates were calculated. Analyses were conducted on the early (within 3 mo) and late (6 mo-2 y) postoperative periods. RESULTS: A total of 201 patients (43.6±8.7 y, 33.3% female) were included. In both early and late postoperative periods, the shorter preoperative symptom duration cohort experienced significantly greater change from preoperative PROM scores compared to the prolonged symptom duration cohort for NDI, VAS-Neck, and VAS-Arm. The shorter symptom duration cohort achieved MCID in the early postoperative period at a significantly higher rate for NDI (78.9% vs. 54.9%, P=0.001), VAS-Neck (87.0% vs. 56.0%, P<0.001), and VAS-Arm (90.5% vs. 70.7%, P=0.002). Prolonged preoperative symptom duration (≥6 mo) was identified as an independent risk factor for failure to achieve MCID at the latest timepoint for NDI (OR: 2.9, 95% CI: 1.2-6.9, P=0.016), VAS-Neck (OR: 9.8, 95% CI: 3.7-26.0, P<0.001), and VAS-Arm (OR: 7.5, 95% CI: 2.5-22.5, P<0.001). CONCLUSIONS: Our study demonstrates improved patient-reported outcomes for those with shorter preoperative symptom duration undergoing CDR for radiculopathy, suggesting delayed surgical intervention may result in poorer outcomes and greater postoperative disability. LEVEL OF EVIDENCE: III.

Predictors for Failure to Respond to Erector Spinae Plane Block Following Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To identify the risk factors associated with failure to respond to erector spinae plane (ESP) block following minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). SUMMARY OF BACKGROUND DATA: ESP block is an emerging opioid-sparing regional anesthetic that has been shown to reduce immediate postoperative pain and opioid demand following MI-TLIF-however, not all patients who receive ESP blocks perioperatively experience a reduction in immediate postoperative pain. METHODS: This was a retrospective review of consecutive patients undergoing 1-level MI-TLIF who received ESP blocks by a single anesthesiologist perioperatively at a single institution. ESP blocks were administered in the OR following induction. Failure to respond to ESP block was defined as patients with a first numerical rating scale (NRS) score post-surgery of >5.7 (mean immediate postoperative NRS score of control cohort undergoing MI TLIF without ESP block). Multivariable logistic regressions were performed to identify predictors for failure to respond to ESP block. RESULTS: A total of 134 patients were included (mean age 60.6 years, 43.3% females). The median and interquartile range (IQR) first pain score post-surgery was 2.5 (0.0-7.5). Forty-nine (36.6%) of patients failed to respond to ESP block. In the multivariable regression analysis, several independent predictors for failure to respond to ESP block following MI TLIF were identified: female sex (OR 2.33, 95% CI 1.04-5.98, P=0.040), preoperative opioid use (OR 2.75, 95% CI 1.03- 7.30, P=0.043), anxiety requiring medication (OR 3.83, 95% CI 1.27-11.49, P=0.017), and hyperlipidemia (OR 3.15, 95% CI 1.31-7.55, P=0.010). CONCLUSIONS: Our study identified several predictors for failure to respond to ESP block following MI TLIF including female sex, preoperative opioid pain medication use, anxiety, and hyperlipidemia. These findings may help inform the approach to counseling patients on perioperative outcomes and pain expectations following MI-TLIF with ESP block. LEVEL OF EVIDENCE: III.

Reliability of Vertebral Pelvic Angles in Assessment of Spinal Alignment.

STUDY DESIGN: Reliability analysis. OBJECTIVES: Vertebral pelvic angles (VPA) are gaining popularity given their ability to describe the shape of the spine. Understanding the reliability and minimal detectable change (MDC) is necessary to determine how these measurement tools should be used in the manual assessment of spine radiographs. Our aim is to assess intra- and interobserver intraclass correlation coefficients (ICC) and the MDC in the use of VPA for assessing alignment in adult spinal deformity (ASD). METHODS: Three independent examiners blindly measured T1, T4, T9, L1, and L4PA twice in ASD patients with a 4-week window after the initial measurements. Patients who had undergone hip or shoulder arthroplasty, fused or transitional vertebrae, or whose hip joints were not visible on radiographs were excluded. Power analysis calculated a minimum sample size of 19. Both intra- and interobserver ICC and MDC, which denotes the smallest detectable change in a true value with 95% confidence, were calculated. RESULTS: Out of the 193 patients, 39 were ultimately included in the study, and 390 measurements were performed by 3 raters. Intraobserver ICC values ranged from .90 to .99. The interobserver ICC was .97, .97, .96, .95, and .92, and the MDC was 5.3°, 5.1°, 4.8°, 4.9°, and 4.1° for T1, T4, T9, L1, and L4PA, respectively. CONCLUSION: All VPAs showed excellent intra- and interobserver reliability, however, the MDC is relatively high compared to typical ranges for VPA values. Therefore, surgeons must be aware that substantial alignment changes may not be detected by a single VPA.

Hypoglossal and Glossopharyngeal Nerve Palsy After Anterior Cervical Decompression and Fusion: A Case Report.

CASE: A 69-year-old man underwent a C3-4 anterior cervical discectomy and fusion and developed postoperative hypoglossal and glossopharyngeal palsies that resolved with symptomatic treatment. CONCLUSION: Cranial nerve palsy is a rare and possibly under-reported injury after higher-level cervical spine surgery. Conscientious positioning and awareness of these nerves during surgical exposure are crucial to minimizing cranial nerve palsies. Proper workup to identify these palsies and differentiate them from other complications is necessary to guide proper treatment.

Limited Improvement With Minimally Invasive Lumbar Decompression Alone for Degenerative Scoliosis With Cobb Angle Over 20°: The Impact of Decompression Location.

STUDY DESIGN: Retrospective review of a prospectively collected multisurgeon registry. OBJECTIVE: To evaluate the outcomes of minimally invasive (MI) decompression in patients with severe degenerative scoliosis (DS) and identify factors associated with poorer outcomes. SUMMARY OF BACKGROUND CONTEXT: MI decompression has gained widespread acceptance as a treatment option for patients with lumbar canal stenosis and DS. However, there is a lack of research regarding the clinical outcomes and the impact of MI decompression location in patients with severe DS exhibiting a Cobb angle exceeding 20°. MATERIALS AND METHODS: Patients who underwent MI decompression alone were included and categorized into the DS or control groups based on Cobb angle (>20°). Decompression location was labeled as "scoliosis-related" when the decompression levels were across or between end vertebrae and "outside" when the operative levels did not include the end vertebrae. The outcomes, including the Oswestry Disability Index (ODI), were compared between the propensity score-matched groups for improvement and minimal clinical importance difference (MCID) achievement at ≥1 year postoperatively. Multivariable regression analysis was conducted to identify factors contributing to the nonachievement of MCID in ODI of the DS group at the ≥1-year time point. RESULTS: A total of 253 patients (41 DS) were included in the study. Following matching for age, sex, osteoporosis status, psoas muscle area, and preoperative ODI, the DS groups exhibited a significantly lower rate of MCID achievement in ODI (DS: 45.5% vs. control 69.0%, P =0.047). The "scoliosis-related" decompression (odds ratio: 9.9, P =0.028) was an independent factor of nonachievement of MCID in ODI within the DS group. CONCLUSIONS: In patients with a Cobb angle >20°, lumbar decompression surgery, even in the MI approach, may result in limited improvement of disability and physical function. Caution should be exercised when determining a surgical plan, especially when decompression involves the level between or across the end vertebrae. LEVEL OF EVIDENCE: 3.

The Impact of Posterior Intervertebral Osteophytes on Patient-Reported Outcome Measures After L5-S1 Anterior Lumbar Interbody Fusion and Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: (1) To develop a reliable grading system to assess the severity of posterior intervertebral osteophytes and (2) to investigate the impact of posterior intervertebral osteophytes on clinical outcomes after L5-S1 decompression and fusion through anterior lumbar interbody fusion (ALIF) and minimally-invasive transforaminal lumbar interbody fusion (MIS-TLIF). BACKGROUND: There is limited evidence regarding the clinical implications of posterior lumbar vertebral body osteophytes for ALIF and MIS-TLIF surgeries and there are no established grading systems that define the severity of these posterior lumbar intervertebral osteophytes. PATIENTS AND METHODS: A retrospective analysis of patients undergoing L5-S1 ALIF or MIS-TLIF was performed. Preoperative and postoperative patient-reported outcome measures of the Oswestry Disability Index (ODI) and leg Visual Analog Scale (VAS) at 2-week, 6-week, 12-week, and 6-month follow-up time points were assessed. Minimal clinically important difference (MCID) for ODI of 14.9 and VAS leg of 2.8 were utilized. Osteophyte grade was based on the ratio of osteophyte length to foraminal width. "High-grade" osteophytes were defined as a maximal osteophyte length >50% of the total foraminal width. RESULTS: A total of 70 consecutive patients (32 ALIF and 38 MIS-TLIF) were included in the study. There were no significant differences between the two cohorts in patient-reported outcome measures or achievement of MCID for Leg VAS or ODI preoperatively or at any follow-ups. On multivariate analysis, neither the surgical approach nor the presence of high-grade foraminal osteophytes was associated with leg VAS or ODI scores at any follow-up time point. In addition, neither the surgical approach nor the presence of high-grade foraminal osteophytes was associated with the achievement of MCID for leg VAS or ODI at 6 months. CONCLUSION: ALIF and MIS-TLIF are both valid options for treating degenerative spine conditions and lumbar radiculopathy, even in the presence of high-grade osteophytes that significantly occupy the intervertebral foramen. LEVEL OF EVIDENCE: 3.

Robot-navigated pedicle screw insertion can reduce intraoperative blood loss and length of hospital stay: analysis of 1,633 patients utilizing propensity score matching.

BACKGROUND CONTEXT: Navigation and robotic technologies have emerged as an alternative option to conventional freehand techniques for pedicle screw insertion. However, the effectiveness of these technologies in reducing the perioperative complications of spinal fusion surgery remains limited due to the small cohort size in the existing literature. PURPOSE: To investigate whether utilization of robotically navigated pedicle screw insertion can reduce the perioperative complications of spinal fusion surgery-including reoperations-with a sizeable cohort. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Patients who underwent primary lumbar fusion surgery between 2019 and 2022. OUTCOME MEASURES: Perioperative complications including readmission, reoperation, its reasons, estimated blood loss, operative time, and length of hospital stay. METHODS: Patients' data were collected including age, sex, race, body mass index, upper-instrumented vertebra, lower-instrumented vertebra, number of screws inserted, and primary procedure name. Patients were classified into the following two groups: freehand group and robot group. The variable-ratio greedy matching was utilized to create the matched cohorts by propensity score and compared the outcomes between the two group. RESULTS: A total of 1,633 patients who underwent primary instrumented spinal lumbar fusion surgery were initially identified (freehand 1,286; robot 347). After variable ratio matching was performed with age, sex, body mass index, fused levels, and upper instrumented vertebrae level, 694 patients in the freehand group and 347 patients in robot groups were selected. The robot group showed less estimated blood loss (418.9±398.9 vs 199.2±239.6 ml; p<.001), shorter LOS (4.1±3.1 vs 3.2±3.0 days; p<.001) and similar operative time (212.5 vs 222.0 minutes; p=.151). Otherwise, there was no significant difference in readmission rate (3.6% vs 2.6%; p=.498), reoperation rate (3.2% vs 2.6%; p=.498), and screw malposition requiring reoperation (five cases, 0.7% vs one case, 0.3%; p=1.000). CONCLUSIONS: Perioperative complications requiring readmission and reoperation were similar between fluoroscopy guided freehand and robotic surgery. Robot-guided pedicle screw insertion can enhance surgical efficiency by reducing intraoperative blood loss and length of hospital stay without extending operative time.

Recovery Kinetics After Cervical Spine Surgery.

STUDY DESIGN: Retrospective review of a prospectively maintained multisurgeon registry. OBJECTIVE: To study recovery kinetics and associated factors after cervical spine surgery. SUMMARY OF BACKGROUND DATA: Few studies have described return to activities cervical spine surgery. This is a big gap in the literature, as preoperative counseling and expectations before surgery are important. MATERIALS AND METHODS: Patients who underwent either anterior cervical discectomy and fusion (ACDF) or cervical disk replacement (CDR) were included. Data collected included preoperative patient-reported outcome measures, return to driving, return to working, and discontinuation of opioids data. A multivariable regression was conducted to identify the factors associated with return to driving by 15 days, return to working by 15 days, and discontinuing opioids by 30 days. RESULTS: Seventy ACDF patients and 70 CDR patients were included. Overall, 98.2% of ACDF patients and 98% of CDR patients returned to driving in 16 and 12 days, respectively; 85.7% of ACDF patients and 90.9% of CDR patients returned to work in 16 and 14 days; and 98.3% of ACDF patients and 98.3% of CDR patients discontinued opioids in a median of seven and six days. Though not significant, minimal (odds ratio (OR)=1.65) and moderate (OR=1.79) disability was associated with greater odds of returning to driving by 15 days. Sedentary work (OR=0.8) and preoperative narcotics (OR=0.86) were associated with decreased odds of returning to driving by 15 days. Medium (OR=0.81) and heavy (OR=0.78) intensity occupations were associated with decreased odds of returning to work by 15 days. High school education (OR=0.75), sedentary work (OR=0.79), and retired/not working (OR=0.69) were all associated with decreased odds of discontinuing opioids by 30 days. CONCLUSIONS: Recovery kinetics for ACDF and CDR are comparable. Most patients return to all activities after ACDF and CDR within 16 days. These findings serve as an important compass for preoperative counseling.

Inducible expression of stem cell associated intermediate filament nestin reveals an important role in glioblastoma carcinogenesis.

The intermediate filament nestin is transiently expressed in neural stem/progenitor cells during the development of central nervous system. Recently, increasing evidence has shown that upregulation of nestin is related to malignancy of several cancers, especially glioblastoma. However, the function of nestin in carcinogenesis remains unclear. In this study, we investigated the role of nestin in glioblastoma carcinogenesis by comparing subclones of rat C6 glioblastoma cells that were either high or low for nestin expression. We found that while nestin expression did not influence the in vitro proliferation of glioblastoma cells, subclones characterized by high levels of nestin formed tumors in vivo at significantly faster rates than subclones with low expression. Importantly, C6 subclones that expressed nestin at low levels in vitro were also found to give rise to tumors highly positive for the protein, suggesting that induction of nestin plays an important role in glioblastoma carcinogenesis. Derivation of nestin positive tumors from nestin negative human U87 glioblastoma cells in immunodeficient mice further confirmed that a switch to positive expression of nestin is fundamental to the course of glioblastoma development. Blocking the expression of nestin in glioblastoma tumors via intratumor injection of shRNA significantly slowed tumor growth and volume. These results demonstrated that nestin plays a crucial role in development of glioblastoma and may potentially be targeted for treatment of the disease.

Management of anaphylaxis in primary care: Canadian expert consensus recommendations.

BACKGROUND: Anaphylaxis is often managed inadequately. We used findings from a systematic review of gaps in anaphylaxis management to develop evidence-based recommendations for gaps rated as clinically important by a panel of Canadian allergy experts. METHODS: The nominal group technique (NGT) consensus methodology was used to develop evidence-based recommendations for the management of anaphylaxis in primary care. Physician-specific gaps from our systematic review were prioritized by consensus meeting participants in two rounds, which involved the rating, discussion, and re-rating of gaps. Using current anaphylaxis guidelines, recommendations were then developed for each category of gaps that were identified by the panel as clinically important. RESULTS: Thirty unique physician gaps from the systematic review were categorized according to gaps of knowledge and anaphylaxis practice behaviors. The panel rated diagnosis of anaphylaxis, and when and how to use epinephrine auto-injectors as clinically important knowledge gaps; and rated infrequent or delayed epinephrine administration, low rate of auto-injector prescription, and infrequent or no referrals to allergy specialists after a reaction as important practice behavior gaps. Evidence from four guidelines was used to support the consensus recommendation statements for three resulting categories of gap themes: anaphylaxis management, epinephrine use, and follow-up care. CONCLUSION: We used an NGT consensus methodology to develop an educational resource for primary care physicians and allergists to better understand how to manage patients with anaphylaxis. Next steps include testing our findings against observed data in primary care settings and to develop other strategies or tools to overcome gaps in anaphylaxis management.

Transforming growth factor beta mimetics: discovery of 7-[4-(4-cyanophenyl)phenoxy]-heptanohydroxamic acid, a biaryl hydroxamate inhibitor of histone deacetylase.

Transforming growth factor beta (TGF-beta) is a multifunctional protein that has been shown to possess potent growth-inhibitory activity. To identify small molecular weight compounds with TGF-beta-like activities, high throughput screening was performed using mink lung epithelial cells stably transfected with a TGF-beta-responsive plasminogen activator inhibitor 1 promoter/luciferase construct. Biaryl hydroxamate compounds were identified that demonstrated TGF-beta-like activities. 7-[4-(4-cyanophenyl)phenoxy]-heptanohydroxamic acid (A-161906) demonstrated complete TGF-beta-like agonist activity in the plasminogen activator inhibitor 1/luciferase construct. A-161906 inhibited the proliferation of multiple cell lines in a concentration-dependent manner. Cells were growth arrested at the G1-S checkpoint similar to TGF-beta. Consistent with the G1-S arrest, A-161906 induced the expression of the cyclin-dependent kinase inhibitor p21waf1/cip1. A-161906 produced many cellular effects similar to that of TGF-beta but did not displace labeled TGF-beta from its receptors. Cells with mutations in either of the TGF-beta receptors I or II were growth-arrested by A-161906. Therefore, the site of action of A-161906 appears to be distal to the receptors and possibly involved with the signaling events controlled by TGF-beta. The TGF-beta mimetic effect of A-161906 can be partially, if not entirely, explained by its activity as a histone deacetylase (HDAC) inhibitor. A-161906 demonstrated potent HDAC-inhibitory activity (IC50 = 9 nM). A-161906 is a novel small molecular weight compound (< 400 MW) having TGF-beta mimetic activity as a result of its potent HDAC-inhibitory activity. These results and those of others demonstrate the importance of HDACs in regulation of the TGF-beta signaling pathway(s).

Allergies in children.

Allergic diseases in children have increased significantly in recent years and now affect up to 35% of children. They are a major cause of morbidity in children. Although there is a genetic predisposition, it is the exposure to environmental allergens, irritants and infections that will determine the sensitization to different dietary and inhalant allergens. As the genetic and environmental factors that act on an immature cellular immune system are better elucidated and their roles established, the implementation of more enduring preventive efforts will be developed. However, at present, the best approach to the child at high risk for the development of allergies is to institute dietary and environmental control measures early to decrease sensitization, and to recognize and appropriately treat the evolving signs and symptoms of allergic disease.

Leucocyte adhesion deficiency presenting as a chronic ileocolitis.

CD11/CD18 leucocyte glycoprotein deficiency is a rare, congenital adhesion molecule disorder which, in its severe form, is usually fatal. Leucocytes in affected subjects have abnormal migration and adherence, rendering patients susceptible to life threatening infections. The CD11/CD18 integrins, and other adhesion molecules, are considered essential to the normal inflammatory response. It has been postulated that adhesion molecules may be responsible for mediating in part, the inflammatory changes observed in inflammatory bowel diseases and related disorders. This report describes the first case of CD11/CD18 deficiency characterised by a chronic ileocolitis. Bone marrow transplantation completely resolved the gastrointestinal symptoms, supporting a role for neutrophil dysfunction in the pathogenesis of the gut lesions. This case suggests that specific blockade of CD11/CD18 integrins alone may not halt the chronic inflammatory response observed in immune mediated bowel disorders, and that abnormalities of leucocyte function must be included in the differential diagnosis of paediatric Crohn's disease.

Distinct patterns of cow's milk allergy in infancy defined by prolonged, two-stage double-blind, placebo-controlled food challenges.

BACKGROUND: The clinical manifestations of cow's milk allergy (CMA) are highly variable, and challenges usually identify only immediate, IgE mediated reactions. OBJECTIVE: To clearly identify CMA of immediate and delayed types using a two-stage, double-blind, placebo-controlled food challenge (DBPCFC), and to prospectively compare the clinical history and analyses of specific IgE antibodies to milk in predicting outcome of DBPCFC. METHODS: A total of 69 patients (33 girls, 36 boys) were recruited for study based on a history highly suggestive of CMA and resolution of symptoms on a bovine protein-free diet. After skin-prick tests (SPTs) and search for allergen-specific serum IgE antibodies by enzyme allergosorbent test (EAST), a two-stage DBPCFC was performed over several days. RESULTS: Of 16 patients (mean age 36.9 months) classified as probable immediate reactors based on the history, 10 (62.5%) had a positive DBPCFC with similar patterns to historical adverse reactions (< or = 2 h after milk exposure). The other 53 (77%) patients (17.3 months) had a history of probable delayed type CMA presenting with predominantly gastrointestimal symptoms from 2 h and up to 6 days after milk exposure. Of these, 15 (28.8%) had a positive DBPCFC, again with a symptom pattern similar to the history. Sensitivity/specificity of SPT was similar to that of EAST for both immediate (70/83% and 62/83% respectively, NS) or delayed (0/97% and 0/97%) CMA confirmed by DBPCFC. CONCLUSIONS: Using our two-stage, prolonged DBPCFC, we clearly identified two groups of children with CMA, reflecting different pathogenesis of either immediate-type IgE-dependent, or delayed-type IgE-independent allergy. Although useful in immediate reactors, IgE antibody determination cannot predict the outcome of DBPCFC in delayed reactors. A thorough clinical history was the most helpful tool to predict the type of response in challenge positive patients.