Impact of surgical risk factors for non-union on lumbar spinal fusion outcomes using cellular bone allograft at 24-months follow-up.

BACKGROUND: The current report investigates fusion rates and patient-reported outcomes following lumbar spinal surgery using cellular bone allograft (CBA) in patients with risk factors for non-union. METHODS: A prospective, open label study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT02969616) to assess fusion success rates and patient-reported outcomes in subjects with risk factors for non-union. Subjects were categorized into low-risk (≤ 1 risk factors) and high-risk (> 1 risk factors) groups. Radiographic fusion status was evaluated by an independent review of dynamic radiographs and CT scans. Patient-reported outcome measures included quality of life (EQ-5D), Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain. Adverse event reporting was conducted throughout 24-months of follow-up. RESULTS: A total of 274 subjects were enrolled: 140 subjects (51.1%) were categorized into the high-risk group (> 1 risk factor) and 134 subjects (48.9%) into the low-risk group (≤ 1 risk factors). The overall mean age at screening was 58.8 years (SD 12.5) with a higher distribution of females (63.1%) than males (36.9%). No statistical difference in fusion rates were observed between the low-risk (90.0%) and high-risk (93.9%) groups (p > 0.05). A statistically significant improvement in patient-reported outcomes (EQ-5D, ODI and VAS) was observed at all time points (p < 0.05) in both low and high-risk groups. The low-risk group showed enhanced improvement at multiple timepoints in EQ-5D, ODI, VAS-Back pain and VAS-Leg pain scores compared to the high-risk group (p < 0.05). The number of AEs were similar among risk groups. CONCLUSIONS: This study demonstrates high fusion rates following lumbar spinal surgery using CBA, regardless of associated risk factors. Patient reported outcomes and fusion rates were not adversely affected by risk factor profiles. TRIAL REGISTRATION: NCT02969616 (21/11/2016).

Twenty-four-month interim results from a prospective, single-arm clinical trial evaluating the performance and safety of cellular bone allograft in patients undergoing lumbar spinal fusion.

BACKGROUND: Autologous bone grafts are the gold standard for spinal fusion; however, harvesting autologous bone can result in donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allografts (CBAs) are a viable alternative that avoids the need for bone harvesting and may increase fusion success alone or when used as an adjunct material. The present study examined the efficacy and safety of CBA when used as an adjunct graft material to lumbar arthrodesis. METHODS: A prospective, single-arm, multicenter clinical trial (NCT02969616) was conducted in adult subjects (> 18 years of age) undergoing lumbar spinal fusion with CBA graft (CBA used as primary (≥ 50% by volume), with augmentation up to 50%). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcomes were assessed with the Oswestry Disability Index (ODI), and Visual Analog Scales (VAS) score for back and leg pain. Adverse events were assessed through the 24-month follow-up period. The presented data represents an analysis of available subjects (n = 86) who completed 24 months of postoperative follow-up at the time the data was locked for analysis. RESULTS: Postoperative 24-month fusion success was achieved in 95.3% of subjects (n = 82/86) undergoing lumbar spinal surgery. Clinical outcomes showed statistically significant improvements in ODI (46.3% improvement), VAS-Back pain (75.5% improvement), and VAS-Leg pain (85.5% improvement) (p < 0.01) scores at Month 24. No subject characteristics or surgical factors were associated with pseudoarthrosis. A favorable safety profile with a limited number of adverse events was observed. CONCLUSIONS: The use of CBA as an adjunct graft material showed high rates of successful lumbar arthrodesis and significant improvements in pain and disability scores. CBA provides an alternative to autograft with comparable fusion success rates and clinical benefits. TRIAL REGISTRATION: NCT02969616.

Using Veterans Socials to Build a Community: Feasibility of the VOICES Intervention.

Increasing social connection and access to care has been found to decrease the rate of suicide in U.S. veterans. The Veteran Outreach Into the Community to Expand Social Support (VOICES) is an intervention developed by Department Veteran Affairs (VA) staff to improve social connection and provide information about services by implementing community-based Veterans Socials. Seventy veterans at eight locations completed an anonymous cross-sectional survey. This evaluation examined three domains, acceptability (i.e., perceived value), demand (i.e., estimated or actual use), and expansion (i.e., sustainability and increase of Veterans Socials across time and locations). Findings indicated considerable levels of acceptability, demand for, and expansion of this intervention. Additionally, data suggested this intervention may increase social connection and utilization of VA services among attendees.

Gene therapy for a murine model of eosinophilic esophagitis.

BACKGROUND: Eosinophils are specialized granulocytic effector cells that store and release highly active mediators used in immune defense. Eosinophils are also implicated in the pathogenesis of allergic disorders, including eosinophilic esophagitis (EoE), a chronic disorder characterized by infiltration of eosinophils into the esophagus and release of mediators that damage tissue, resulting in gastrointestinal morbidity, food impaction, and dysphagia. Treatment with elimination diets and/or topical corticosteroid therapy slow disease progression, but are complicated by adverse effects, limited compliance, and loss of response to therapy. We hypothesized that a single administration of an adeno-associated virus (AAV) coding for an anti-eosinophil monoclonal antibody that induces eosinophil clearance (anti-Siglec-F) would treat on a persistent basis a murine model of EoE. METHODS: A mouse model of peanut-induced EoE that mimics the human disease was established by sensitization and challenge with peanut extract. After challenge, these mice exhibited an EoE phenotype demonstrated by elevated levels of blood eosinophils, infiltration of eosinophils in the esophagus with associated esophageal remodeling and food impaction. RESULTS: The mice were treated with a single intravenous administration (1011 genome copies) of AAVrh.10mAnti-Eos, a serotype rh.10 AAV vector coding for an anti-Siglec-F monoclonal antibody. Vector administration resulted in persistent, high levels of anti-Siglec-F antibody expression. Administration of AAVrh.10mAnti-Eos to the mouse model of EoE reduced blood (P < 0.02) and esophageal eosinophil numbers (P < 0.002) protected from esophageal tissue remodeling and minimized food impaction. CONCLUSION: These results suggest that a single treatment with AAVrh.10mAnti-Eos has the potential to provide persistent therapeutic benefit to patients with EoE.

Gene therapy for C1 esterase inhibitor deficiency in a Murine Model of Hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a life-threatening, autosomal dominant disorder characterized by unpredictable, episodic swelling of the face, upper airway, oropharynx, extremities, genitalia, and gastrointestinal tract. Almost all cases of HAE are caused by mutations in the SERPING1 gene resulting in a deficiency in functional plasma C1 esterase inhibitor (C1EI), a serine protease inhibitor that normally inhibits proteases in the contact, complement, and fibrinolytic systems. Current treatment of HAE includes long-term prophylaxis with attenuated androgens or human plasma-derived C1EI and management of acute attacks with human plasma-derived or recombinant C1EI, bradykinin, and kallikrein inhibitors, each of which requires repeated administration. As an approach to effectively treat HAE with a single treatment, we hypothesized that a one-time intravenous administration of an adeno-associated virus (AAV) gene transfer vector expressing the genetic sequence of the normal human C1 esterase inhibitor (AAVrh.10hC1EI) would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes. METHODS: To study the efficacy of AAVrh.10hC1EI, we used CRISPR/Cas9 technology to create a heterozygote C1EI-deficient mouse model (S63±) that shares characteristics associated with HAE in humans including decreased plasma C1EI and C4 levels. Phenotypically, these mice have increased vascular permeability of skin and internal organs. RESULTS: Systemic administration of AAVrh.10hC1EI to the S63± mice resulted in sustained human C1EI activity levels above the predicted therapeutic levels and correction of the vascular leak in skin and internal organs. CONCLUSION: A single treatment with AAVrh.10hC1EI has the potential to provide long-term protection from angioedema attacks in affected individuals.

Correction to: Veteran Coffee Socials: A Community-Building Strategy for Enhancing Community Reintegration of Veterans.

The original version of this article unfortunately contained a mistake in co-author name and his affiliation. The author name should be Anthony Russo instead it was published as Antony Russo and his affiliation has been corrected.

Veteran Coffee Socials: A Community-Building Strategy for Enhancing Community Reintegration of Veterans.

Veterans transitioning from military to civilian life are vulnerable to a loss of social support and an increase in isolation from their communities, which can exacerbate other difficulties they may be experiencing, such as physical or mental health problems. Veteran Coffee Socials are an innovative community-building pilot intervention designed to foster social support and community between veterans. In seven target communities, certified peer specialists initiated and facilitated weekly "Veteran Coffee Socials"-open peer support groups for veterans, held in local coffee shop or restaurants. Over a 9-month period, an average of 8.5 veterans attended each meeting, for a total of 2236 veteran engagements across seven towns. A range of activities were identified as commonly occurring during these Veteran Coffee Socials. Veteran attendees routinely formed relationships with each other, representatives from community organizations, and staff from local and VA healthcare resources. One of the most common activities involved veterans receiving information and directions for enrollment into needed healthcare supports and to local community resources. Case descriptions are provided illustrate the potential positive impact of this intervention to build community and expand social support for returning veterans through the examination of three individual and three group examples.

High Lumbar Spinal Fusion Rates Using Cellular Bone Allograft Irrespective of Surgical Approach.

BACKGROUND: Mounting evidence demonstrates a promising safety and efficacy profile for spinal fusion procedures using cellular bone allograft (CBA). However, limited data exists on fusion outcomes stratified by surgical approach. The current study investigates the effectiveness of CBA in lumbar spinal fusion by surgical approach (ie, anterior, lateral, and posterior approaches). METHODS: Patients undergoing lumbar spinal fusion with CBA (Trinity Elite) were enrolled into a prospective, multi-center, open-label clinical study (NCT02969616). Fusion status was assessed by an independent review of dynamic radiographs and computed tomography images. Clinical outcome measures included quality of life (QoL; EQ5D), disability (Oswestry Disability Index [ODI]), and pain (visual analog scale [VAS]) for back pain and leg pain). Patient data extending to 24 months were analyzed in a post-hoc analysis. RESULTS: A total of 252 patients underwent interbody fusion (159 women; 93 men). Patients had a mean age of 58.3 years (SD 12.5), height of 168.3 cm (SD 10.2), and weight of 87.3 kg (SD 20.0) with a body mass index of 30.8 kg/m2 (SD 6.5). At 12 months, the overall fusion success rate for bridging bone was 98.5%; fusion success was 98.1%, 100.0%, and 97.9% for anterior, lateral, and posterior approaches, respectively. At 24 months, the overall fusion success rate for bridging bone was 98.9%; fusion success was 97.9%, 100.0%, and 98.8% for anterior, lateral, and posterior approaches, respectively. The surgical approach did not significantly impact fusion success. A significant (P < 0.0001) improvement in QoL, pain, and disability scores was also observed. Significant differences in the ODI, VAS, and EQ5D were observed between the treatment groups (P < 0.05). CONCLUSIONS: CBA represents an attractive alternative to autograft alone, reporting a high rate of successful fusion and clinical outcomes across various surgical approaches. CLINICAL RELEVANCE: The use of CBA for spinal fusion procedures, regardless of surgical approach, provides high rates of fusion with a favorable safety profile and improved patient outcomes. TRIAL REGISTRATION: NCT02969616.

Intestinal epithelial Toll-like receptor 4 regulates goblet cell development and is required for necrotizing enterocolitis in mice.

BACKGROUND & AIMS: Little is known about factors that regulate intestinal epithelial differentiation; microbial recognition receptors such as Toll-like receptor (TLR)4 might be involved. We investigated whether intestinal TLR4 regulates epithelial differentiation and is involved in development of necrotizing enterocolitis (NEC) of the immature intestine. METHODS: Mice with conditional disruption of TLR4 in the intestinal epithelium and TLR4 knockout (TLR4(-/-)) mice were generated by breeding TLR4(loxp/loxp) mice with villin-cre and Ella-cre, respectively. Enterocytes that did not express or overexpressed TLR4 were created by lentiviral or adenoviral transduction. Intestinal organoids were cultured on tissue matrices. Bile acids were measured by colorimetric assays, and microbial composition was determined by 16S pyrosequencing. NEC was induced in 7- to 10-day-old mice by induction of hypoxia twice daily for 4 days. RESULTS: TLR4(-/-) mice and mice with enterocyte-specific deletion of TLR4 were protected from NEC; epithelial differentiation into goblet cells was increased via suppressed Notch signaling in the small intestinal epithelium. TLR4 also regulates differentiation of goblet cells in intestinal organoid and enterocyte cell cultures; differentiation was increased on deletion of TLR4 and restored when TLR4 was expressed ectopically. TLR4 signaling via Notch was increased in intestinal tissue samples from patients with NEC, and numbers of goblet cells were reduced. 16S pyrosequencing revealed that wild-type and TLR4-deficient mice had similar microbial profiles; increased numbers of goblet cells were observed in mice given antibiotics. TLR4 deficiency reduced levels of luminal bile acids in vivo, and addition of bile acids to TLR4-deficient cell cultures prevented differentiation of goblet cells. CONCLUSIONS: TLR4 signaling and Notch are increased in intestinal tissues of patients with NEC and required for induction of NEC in mice. TLR4 prevents goblet cell differentiation, independently of the microbiota. Bile acids might initiate goblet cell development.

COVID-19 and Subsequent Development of Pancytopenia With Concurrent Disseminated Intravascular Coagulation.

Complications resulting from coronavirus disease 2019 (COVID-19) sequelae have been well documented. These include blood conditions such as lymphopenia, thrombocytopenia, and hypercoagulability. Less common problems that may arise are disseminated intravascular coagulation (DIC), immune thrombocytopenic purpura (ITP), and pancytopenia. Furthermore, the majority of COVID-19 patients to develop pancytopenia have been immunosuppressed. We present a case of a previously immunocompetent patient who subsequently developed pancytopenia, DIC, as well as symptoms of ITP one month after being diagnosed with COVID-19.

Twelve-Month Results from a Prospective Clinical Study Evaluating the Efficacy and Safety of Cellular Bone Allograft in Subjects Undergoing Lumbar Spinal Fusion.

BACKGROUND: While autologous bone grafts remain the gold standard for spinal fusion procedures, harvesting autologous bone is associated with significant complications, including donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allograft (CBA) presents an alternative to autologous bone harvesting, with a favorable efficacy and safety profile. The current study further investigates CBA as an adjunct to lumbar spinal fusion procedures. METHODS: A prospective, multicenter, open-label clinical study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT02969616). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcome measures included the Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg pain. Adverse-event reporting was conducted throughout 12 months of follow-up. Available subject data at 12 months were analyzed. RESULTS: A total of 274 subjects were enrolled into the study, with available data from 201 subjects (73.3%) who completed 12 months of postoperative radiographic and clinical evaluation at the time of analysis. Subjects had a mean age of 60.2 ± 11.5 years. A higher number of women (n = 124, 61.7%) than men (n = 77, 38.3%) were enrolled, with a collective mean BMI of 30.6 + 6.5 kg/m2 (range 18.0-51.4). At month 12, successful fusion was achieved in 90.5% of subjects. A significant (p < 0.001) improvement in ODI, VAS-back, and VAS-leg clinical outcomes was also observed compared to baseline scores. One adverse event related to CBA (postoperative radiculopathy) was reported, with surgical exploration demonstrating interbody extrusion of graft material. This subject reported successful fusion at month 12. CONCLUSIONS: CBA represents a viable substitute for harvesting of autograft alone with a high rate of successful fusion and significant improvements in subject-reported outcomes, such as pain and disability. Positive benefit was observed in subjects reporting single and multiple risk factors for pseudoarthrosis.

Gene therapy in a murine model of chronic eosinophilic leukemia-not otherwise specified (CEL-NOS).

Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare, aggressive, fatal disease characterized by blood eosinophilia and dysfunction of organs infiltrated with eosinophils. Clinically, the disease manifests with weight loss, cough, weakness, diarrhea, and multi-organ dysfunction that is unresponsive to therapy. We developed a one-time gene therapy for CEL-NOS using an adeno-associated virus (AAV) expressing an anti-eosinophil monoclonal antibody (AAVrh.10mAnti-Eos) to provide sustained suppression of eosinophil numbers in blood, thus reducing eosinophil tissue invasion and organ dysfunction. A novel CEL-NOS model was developed in NOD-scid IL2rγnull (NSG) mice by administration of AAV expressing the cytokine IL5 (AAVrh.10mIL5), resulting in marked peripheral and tissue eosinophilia of the heart, lung, liver, and spleen, and eventually death. Mice were administered AAVrh.10mAnti-Eos (1011 genome copies) 4 wk after administration of AAVrh.10mIL5 and evaluated for anti-eosinophil antibody expression, blood eosinophil counts, organ eosinophil invasion, and survival. AAVrh.10mAnti-Eos expressed persistent levels of the anti-eosinophil antibody for >24 wk. Strikingly, CEL-NOS treated mice had markedly lower blood eosinophil levels and reduced mortality when compared with control treated mice. These results suggest that a single treatment with AAVrh.10mAnti-Eos has the potential to provide substantial therapeutic benefit to patients with CEL-NOS, a fatal malignant disorder.

DNA attenuates enterocyte Toll-like receptor 4-mediated intestinal mucosal injury after remote trauma.

Intestinal mucosal injury occurs after remote trauma although the mechanisms that sense remote injury and lead to intestinal epithelial disruption remain incompletely understood. We now hypothesize that Toll-like receptor 4 (TLR4) signaling on enterocytes after remote injury, potentially through the endogenous TLR4 ligand high-mobility group box-1 (HMGB1), could lead to intestinal dysfunction and bacterial translocation and that activation of TLR9 with DNA could reverse these effects. In support of this hypothesis, exposure of TLR4-expressing mice to bilateral femur fracture and systemic hypotension resulted in increased TLR4 expression and signaling and disruption of the ileal mucosa, leading to bacterial translocation, which was not observed in TLR4-mutant mice. TLR4 signaling in enterocytes, not immune cells, was required for this effect, as adenoviral-mediated inhibition of TLR4 in enterocytes prevented these findings. In seeking to identify the endogenous TLR4 ligands involved, the expression of HMGB1 was increased in the intestinal mucosa after injury in wild-type, but not TLR4-mutant, mice, and administration of anti-HMGB1 antibodies reduced both intestinal mucosal TLR4 signaling and bacterial translocation after remote trauma. Strikingly, mucosal injury was significantly increased in TLR9-mutant mice, whereas administration of exogenous DNA reduced the extent of TLR4-mediated enterocyte apoptosis, restored mucosal healing, and maintained the histological integrity of the intestinal barrier after remote injury. Taken together, these findings identify a novel link between remote injury and enterocyte TLR4 signaling leading to barrier injury, potentially through HMGB1 as a ligand, and demonstrate the reversal of these adverse effects through activation of TLR9.

Toll-like receptor-4 inhibits enterocyte proliferation via impaired beta-catenin signaling in necrotizing enterocolitis.

BACKGROUND & AIMS: Necrotizing enterocolitis (NEC), the leading cause of gastrointestinal death from gastrointestinal disease in preterm infants, is characterized by exaggerated TLR4 signaling and decreased enterocyte proliferation through unknown mechanisms. Given the importance of beta-catenin in regulating proliferation of many cell types, we hypothesize that TLR4 impairs enterocyte proliferation in NEC via impaired beta-catenin signaling. METHODS: Enterocyte proliferation was detected in IEC-6 cells or in ileum or colon from wild-type, TLR4-mutant, or TLR4(-/-) mice after induction of NEC or endotoxemia. beta-Catenin signaling was assessed by cell fractionation or immunoconfocal microscopy to detect its nuclear translocation. Activation and inhibition of beta-catenin were achieved via cDNA or small interfering RNA, respectively. TLR4 in the intestinal mucosa was inhibited with adenoviruses expressing dominant-negative TLR4. RESULTS: TLR4 activation significantly impaired enterocyte proliferation in the ileum but not colon in newborn but not adult mice and in IEC-6 enterocytes. beta-Catenin activation reversed these effects in vitro. To determine the mechanisms involved, TLR4 activation phosphorylated the upstream inhibitory kinase GSK3beta, causing beta-catenin degradation. NEC in both mouse and humans was associated with decreased beta-catenin and increased mucosal GSK3beta expression. Strikingly, the inhibition of enterocyte beta-catenin signaling in NEC could be reversed, and enterocyte proliferation restored, through adenoviral-mediated inhibition of TLR4 signaling in the small intestinal mucosa. CONCLUSION: We now report a novel pathway linking TLR4 with inhibition of beta-catenin signaling via GSK3beta activation, leading to reduced enterocyte proliferation in vitro and in vivo. These data provide additional insights into the pathogenesis of diseases of intestinal inflammation such as NEC.

Nucleotide-binding oligomerization domain-2 inhibits toll-like receptor-4 signaling in the intestinal epithelium.

BACKGROUND & AIMS: Factors that regulate enterocyte apoptosis in necrotizing enterocolitis (NEC) remain incompletely understood, although Toll-like receptor-4 (TLR4) signaling in enterocytes plays a major role. Nucleotide-binding oligomerization domain-2 (NOD2) is an immune receptor that regulates other branches of the immune system, although its effects on TLR4 in enterocytes and its role in NEC remain unknown. We now hypothesize that activation of NOD2 in the newborn intestine inhibits TLR4, and that failure of NOD2 signaling leads to NEC through increased TLR4-mediated enterocyte apoptosis. METHODS: The effects of NOD2 on enterocyte TLR4 signaling and intestinal injury and repair were assessed in enterocytes lacking TLR4 or NOD2, in mice with intestinal-specific wild-type or dominant-negative TLR4 or NOD2, and in mice with NEC. A protein array was performed on NOD2-activated enterocytes to identify novel effector molecules involved. RESULTS: TLR4 activation caused apoptosis in newborn but not adult small intestine or colon, and its intestinal expression was influenced by NOD2. NOD2 activation inhibited TLR4 in enterocytes, but not macrophages, and reversed the effects of TLR4 on intestinal mucosal injury and repair. Protection from TLR4-induced enterocyte apoptosis by NOD2 required a novel pathway linking NOD2 with the apoptosis mediator second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low PI (SMAC-DIABLO), both in vitro and in vivo. Strikingly, activation of NOD2 reduced SMAC-DIABLO expression, attenuated the extent of enterocyte apoptosis, and reduced the severity of NEC. CONCLUSIONS: These findings reveal a novel inhibitory interaction between TLR4 and NOD2 signaling in enterocytes leading to the regulation of enterocyte apoptosis and suggest a therapeutic role for NOD2 in the protection of intestinal diseases such as NEC.

Intestinal stem cells and their roles during mucosal injury and repair.

The ability of the host to respond to intestinal injury requires the regeneration of native tissue through a highly orchestrated response from the intestinal stem cells, a population of cells located within the intestinal crypts that have the capability to repopulate the entire villous. The field of intestinal stem cell biology is thus of great interest to surgeons and non-surgeons alike, given its relevance to diseases of intestinal injury and inflammation such as inflammatory bowel disease, trauma, and necrotizing enterocolitis. The field of intestinal stem cell research has been advanced recently by the identification of the putative marker, Lgr5, which has allowed for the isolation and further characterization of the intestinal stem cell. Under the control of the WNT signaling pathway, Lgr5 marks the rapidly dividing cells of the intestinal crypt, and identifies a population of cells that is capable of regenerating the entire villous. We now review the identification of Lgr5 as an intestinal stem cell marker, identify controversies in the intestinal stem cell field, and highlight the response of the intestinal stem cell to injury within the intestinal mucosa that may occur clinically.

Minimally invasive transforaminal lumbar interbody fusion with expandable articulating interbody spacers significantly improves radiographic outcomes compared to static interbody spacers.

BACKGROUND: The goal of minimally invasive transforaminal lumbar interbody fusion (MI TLIF) is to restore and maintain disc height and lordosis until arthrodesis occurs, while minimizing muscle disruption and improving recovery time. The purpose of this study was to compare the radiographic outcomes in patients treated with an articulating expandable spacer in MI TLIF to more traditional static spacers. METHODS: This was a multi-site, multi-surgeon, Institutional Review Board-exempt, retrospective clinical study from a prospectively collected database. It included 48 patients with a diagnosis of degenerative disc disease (DDD) at one level from L2 to S1 with or without Grade 1 spondylolisthesis who underwent MI TLIF using either an articulating expandable or static interbody spacer. Twenty-seven patients were in the banana-shaped articulating expandable interbody spacer (ALTERA®, Globus Medical, Inc., Audubon, PA, USA) group, while 21 patients were in the static interbody spacer group. Both groups had supplemental posterior pedicle screw and rod fixation. Radiographic records were assessed for disc height, neuroforaminal height, and lordosis at baseline, 3 and 6 months, and final follow-up. RESULTS: The articulating expandable spacer group displayed significantly greater improvement in anterior disc height from baseline compared to the static spacer group at 6 weeks, 3 and 6 months, and final follow-up by averages of 2.6 mm (79%), 2.8 mm (92%), 3.4 mm (105%), and 3.8 mm (139%), respectively (P<0.05). Mean increases in posterior disc height were significantly greater in the expandable group compared to the static group by 1.2 mm (65%) and 1.7 mm (104%) at 6 months and final follow-up, respectively (P<0.05). Articulating expandable spacers produced significantly greater average improvement by 4.0 mm in neuroforaminal height from baseline to final follow-up compared to static spacers (P<0.05). Increases in intervertebral angle from baseline were significantly greater in the expandable group than in the static group at 3 and 6 months, and final follow-up by averages of 2.5°, 2.8°, and 3.1°, respectively (P<0.05). The articulating expandable spacer group resulted in significantly greater improvements in lumbar lordosis from baseline to 3 and 6 months than the static spacer group by 4.4° and 4.0°, respectively (P<0.05). CONCLUSIONS: MI TLIF with articulating expandable interbody spacers provides significant restoration and maintenance of disc height, neuroforaminal height, and lordosis compared to static spacers in this comparative cohort. Long-term clinical outcomes are needed to correlate with these radiographic improvements.

Multidrug-resistant Salmonella isolates from retail chicken meat compared with human clinical isolates.

AIM: To examine the prevalence of antimicrobial-resistant Salmonella in chicken meat and correlate with isolates from ill humans. METHODS: We isolated Salmonella from raw chicken purchased from a randomly selected sample of retail outlets in central Pennsylvania during 2006-2007. Salmonella isolates from meat were compared, using pulsed-field gel electrophoresis, to isolates in the PulseNet database of Salmonella recovered from humans. RESULTS: Of 378 chicken meat samples, 84 (22%) contained Salmonella. Twenty-six (31%) of the Salmonella isolates were resistant to > or = 3 antimicrobials and 18 (21%) were resistant to ceftiofur. All ceftiofur-resistant isolates exhibited reduced susceptibility (minimum inhibitory concentration >2 microg/mL) to ceftriaxone and carried a bla(CMY) gene, as detected by polymerase chain reaction. Among the 28 Salmonella serovar Typhimurium isolates, 20 (71.4%) were resistant to > or = 3 antimicrobials and 12 (42.9%) were resistant to ceftiofur. One ceftiofur-resistant Salmonella serovar Typhimurium poultry isolate exhibited a rare pulsed-field gel electrophoresis pattern indistinguishable from a human isolate in PulseNet; both isolates carried the bla(CMY-2) gene. CONCLUSIONS: These data demonstrate the presence of multidrug-resistant Salmonella in poultry meat, including bla(CMY) plasmid-mediated genes that confer resistance to both ceftiofur, used in poultry, and ceftriaxone, used for treating salmonellosis in humans. This study illustrates the potential for molecular subtyping databases to identify related Salmonella isolates from meat and ill humans, and suggests that chicken could be a source for multidrug-resistant salmonellosis in humans.

Deer sausage: a newly identified vehicle of transmission of Escherichia coli O157:H7.

Five Missouri patients infected with Escherichia coli O157:H7 were studied for an epidemiologically plausible association. Case isolates, case interviews, and pathogen and meat XbaI pulsed field electrophoresis patterns were consistent with the common source being contaminated, fermented deer sausage, a previously unrecognized mode of transmission for Escherichia coli O157:H7.