Increasing the Dye Payload of Cetuximab-IRDye800CW Enables Photodynamic Therapy.

Cetuximab (Cet)-IRDye800CW, among other antibody-IRDye800CW conjugates, is a potentially effective tool for delineating tumor margins during fluorescence image-guided surgery (IGS). However, residual disease often leads to recurrence. Photodynamic therapy (PDT) following IGS is proposed as an approach to eliminate residual disease but suffers from a lack of molecular specificity for cancer cells. Antibody-targeted PDT offers a potential solution for this specificity problem. In this study, we show, for the first time, that Cet-IRDye800CW is capable of antibody-targeted PDT in vitro when the payload of dye molecules is increased from 2 (clinical version) to 11 per antibody. Cet-IRDye800CW (1:11) produces singlet oxygen, hydroxyl radicals, and peroxynitrite upon activation with 810 nm light. In vitro assays on FaDu head and neck cancer cells confirm that Cet-IRDye800CW (1:11) maintains cancer cell binding specificity and is capable of inducing up to ∼90% phototoxicity in FaDu cancer cells. The phototoxicity of Cet-IRDye800CW conjugates using 810 nm light follows a dye payload-dependent trend. Cet-IRDye800CW (1:11) is also found to be more phototoxic to FaDu cancer cells and less toxic in the dark than the approved chromophore indocyanine green, which can also act as a PDT agent. We propose that antibody-targeted PDT using high-payload Cet-IRDye800CW (1:11) could hold potential for eliminating residual disease postoperatively when using sustained illumination devices, such as fiber optic patches and implantable surgical bed balloon applicators. This approach could also potentially be applicable to a wide variety of resectable cancers that are amenable to IGS-PDT, using their respective approved full-length antibodies as a template for high-payload IRDye800CW conjugation.

PD-L1 Immune Checkpoint Targeted Photoactivable Liposomes (iTPALs) Prime the Stroma of Pancreatic Tumors and Promote Self-Delivery.

Desmoplasia in pancreatic ductal adenocarcinoma (PDAC) limits the penetration and efficacy of therapies. It has been previously shown that photodynamic priming (PDP) using EGFR targeted photoactivable multi-inhibitor liposomes remediates desmoplasia in PDAC and doubles overall survival. Here, bifunctional PD-L1 immune checkpoint targeted photoactivable liposomes (iTPALs) that mediate both PDP and PD-L1 blockade are presented. iTPALs also improve phototoxicity in PDAC cells and induce immunogenic cell death. PDP using iTPALs reduces collagen density, thereby promoting self-delivery by 5.4-fold in collagen hydrogels, and by 2.4-fold in syngeneic CT1BA5 murine PDAC tumors. PDP also reduces tumor fibroblast content by 39.4%. Importantly, iTPALs also block the PD-1/PD-L1 immune checkpoint more efficiently than free α-PD-L1 antibodies. Only a single sub-curative priming dose using iTPALs provides 54.1% tumor growth inhibition and prolongs overall survival in mice by 42.9%. Overall survival directly correlates with the extent of tumor iTPAL self-delivery following PDP (Pearson's r = 0.670, p = 0.034), while no relationship is found for sham non-specific IgG constructs activated with light. When applied over multiple cycles, as is typical for immune checkpoint therapy, PDP using iTPALs promises to offer durable tumor growth delay and significant survival benefit in PDAC patients, especially when used to promote self-delivery of integrated chemo-immunotherapy regimens.

Comparison of clinical outcomes in patients undergoing one- and two-level minimally invasive lumbar microdiscectomy.

OBJECTIVE: Herniated nucleus pulposus (HNP) is one of the most common lumbar spine conditions treated surgically, often through a minimally invasive surgery (MIS) microdiscectomy approach. This technique attempts to reduce damage to the paraspinal muscular-ligamentous envelope. However, there are currently limited data regarding comparative outcomes using patient-reported outcome measures (PROMs) for one- and two-level MIS discectomies. The aim of this study was to quantify comparative clinical outcomes in patients undergoing one-level and two-level MIS lumbar microdiscectomy for HNP using PROMs. METHODS: The authors performed a retrospective review of patients undergoing MIS lumbar microdiscectomy between 2004 and 2019 for the primary diagnosis of HNP at a single academic institution. All patients had a minimum 1-year follow-up. Patient demographics and comorbidities were collected to establish baselines between cohorts. PROMs and minimal clinically important differences (MCIDs) were used to examine the patient's perception of operative success. Bivariate and multivariate linear/logistic regression analyses were used to compare one- and two-level discectomies. The bivariate analysis included the t-test and chi-square test, which were used to assess continuous and categorical variables, respectively. Statistical significance was established at p < 0.05. RESULTS: A total of 293 patients underwent one-level (n = 250) or two-level (n = 43) MIS discectomies. The mean follow-ups for the one- and two-level cohorts were 50.4 (SD 35.5) months and 61.6 (SD 39.8) months, respectively. Fewer female patients underwent two-level discectomies, and BMI and operative duration were higher in the two-level group (p < 0.001). Recurrent herniation requiring reoperation was recorded at rates of 6.80% and 11.6% in the one- and two-level groups, respectively (p = 0.270). Pre- and postoperative PROMs were largely similar between the cohorts; however, patients undergoing one-level discectomy had greater improvement in leg pain, and a significantly greater proportion of these patients achieved MCID for the leg pain visual analog scale score (p < 0.001). CONCLUSIONS: At the 1-year clinical follow-up, patients who underwent two-level discectomy had significantly less improvement in leg pain scores with lower achievement of MCID for leg pain improvement than patients undergoing one-level procedures. At the 1-year follow-up, there were no other significant differences in PROMs between the two cohorts. Given these findings, patients should be counseled regarding the anticipated outcomes to better manage expectations. Further studies are warranted to examine the long-term clinical outcomes associated with single- and multilevel MIS discectomy.

A single photodynamic priming protocol augments delivery of ⍺-PD-L1 mAbs and induces immunogenic cell death in head and neck tumors.

Photodynamic priming (PDP) leverages the photobiological effects of subtherapeutic photodynamic therapy (PDT) regimens to modulate the tumor vasculature and stroma. PDP also sensitizes tumors to secondary therapies, such as immunotherapy by inducing a cascade of molecular events, including immunogenic cell death (ICD). We and others have shown that PDP improves the delivery of antibodies, among other theranostic agents. However, it is not known whether a single PDP protocol is capable of both inducing ICD in vivo and augmenting the delivery of immune checkpoint inhibitors. In this rapid communication, we show for the first time that a single PDP protocol using liposomal benzoporphyrin derivative (Lipo-BPD, 0.25 mg/kg) with 690 nm light (75 J/cm2 , 100 mW/cm2 ) simultaneously doubles the delivery of ⍺-PD-L1 antibodies in murine AT-84 head and neck tumors and induces ICD in vivo. ICD was observed as a 3-11 fold increase in tumor cell exposure of damage-associated molecular patterns (Calreticulin, HMGB1, and HSP70). These findings suggest that this single, highly translatable PDP protocol using clinically relevant Lipo-BPD holds potential for improving immunotherapy outcomes in head and neck cancer. It can do so by simultaneously overcoming physical barriers to the delivery of immune checkpoint inhibitors, and biochemical barriers that contribute to immunosuppression.

Short-term and Long-term Complications of Cervical Disc Arthroplasty.

STUDY DESIGN: A narrative review. OBJECTIVE: This review discusses the short and long-term complications associated with cervical disc arthroplasty (CDA). SUMMARY OF BACKGROUND DATA: CDA is a safe and effective motion-sparing alternative to fusion for the treatment of cervical disc pathology in patients with cervical radiculopathy or myelopathy. Although CDA offers advantages over fusion within a narrower set of indications, it introduces new technical challenges and potential complications. METHODS: A systematic search of several large databases, including Cochrane Central, PubMed, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry, was conducted from January 2005 to August 2023 to identify published studies and clinical trials evaluating cervical disc replacement complications and outcomes. RESULTS: Short-term complications are primarily related to surgical approach and include dysphagia reported as high as ~70%, laryngeal nerve injury ~0%-1.25%, Horner syndrome ~0.06%, hematoma ~0.01%, gross device extrusion ~0.3%, whereas long-term complications include adjacent segment disease reported at ~3.8%, osteolysis ~44%-64%, heterotopic ossification ~7.3%-69.2%, implant failure ~3.3%-3.7%, and implant wear, which varies depending on design. CONCLUSIONS: Approaches for mitigating complications broadly include meticulous dissection, intraoperative techniques, and diligent postoperative follow-up. This review emphasizes the need for a comprehensive understanding and management of complications to enhance the safety, reproducibility, and success of CDA. As CDA continues to evolve, there remains a critical need for ongoing research to delve deeper into evaluating risk for complications and long-term patient outcomes.

Increased cage angle effects on radiographic outcomes after stand-alone anterior lumbar interbody fusion.

OBJECTIVE: Anterior lumbar interbody fusion (ALIF) is a well-accepted surgical technique used to treat various lumbar degenerative pathologies. Recently, hyperlordotic cages have been introduced to create higher degrees of lordosis to the lumbar spine. There are little data currently available to define the radiographic benefits that these cages provide with stand-alone ALIF. The goal of the present study was to assess the effect of increasing cage angles on postoperative subsidence, sagittal alignment, and foraminal and disc height in patients who underwent single-level stand-alone ALIF surgery. METHODS: A retrospective cohort study was performed of consecutive patients who underwent single-level ALIF by a single spine surgeon. Radiographic analysis included global lordosis, operative level of segmental lordosis, cage subsidence, sacral slope, pelvic tilt, pelvic incidence, pelvic incidence-lumbar lordosis mismatch, edge loading, foraminal height, posterior disc height, anterior disc height, and adjacent-level lordosis. Multivariate linear and logistic regressions were performed to analyze the relationship between cage angle and radiographic outcomes. RESULTS: Seventy-two patients were included in the study and divided into three groups based on cage angle: < 10° (n = 17), 10°-15° (n = 36), and > 15° (n = 19). Within the entire study cohort, there were significant improvements in disc and foraminal height, as well as segmental and global lordosis, at the final follow-up after single-level ALIF. However, when stratified by cage angle groups, patients with > 15° cages did not have any additional significant changes in global or segmental lordosis compared with those patients with smaller cage angles, but patients with > 15° cages showed greater risk of subsidence while also having significantly less improvements in foraminal height, posterior disc height, and average disc height compared with the other groups. CONCLUSIONS: Patients with < 15° stand-alone ALIF cages showed improved average foraminal and disc (posterior, anterior, and average) height without sacrificing improvements in sagittal parameters or increasing risk of subsidence when compared to patients with hyperlordotic cages. The use of hyperlordotic cages > 15° did not provide spinal lordosis commensurate with the lordotic angle of the cage and had a greater risk of subsidence. Although this study was limited by a lack of patient-reported outcomes to correlate with radiographic results, these findings support the judicious use of hyperlordotic cages in stand-alone ALIF.

Rates of Postoperative Complications and Approach-related Neurological Symptoms After L4-L5 Lateral Transpsoas Lumbar Interbody Fusion Compared With Upper Lumbar Levels.

STUDY DESIGN: This was a retrospective comparative study. OBJECTIVE: To compare the likelihood of approach-related complications for patients undergoing single-level lateral lumbar interbody fusion (LLIF) at L4-L5 to those undergoing the procedure at upper lumbar levels. SUMMARY OF BACKGROUND DATA: LLIF has been associated with a number of advantages when compared with traditional interbody fusion techniques. However, potential risks with the approach include vascular or visceral injury, thigh dysesthesias, and lumbar plexus injury. There are concerns of a higher risk of these complications at the L4-L5 level compared with upper lumbar levels. MATERIALS AND METHODS: A retrospective cohort review was completed for consecutive patients undergoing single-level LLIF between 2004 and 2019 by a single surgeon. Indication for surgery was symptomatic degenerative lumbar stenosis and/or spondylolisthesis. Patients were divided into 2 cohorts: LLIF at L4-L5 versus a single level between L1 and L4. Baseline characteristics, intraoperative complications, postoperative approach-related neurological symptoms, and patient-reported outcomes were compared and analyzed between the cohorts. RESULTS: A total of 122 were included in analysis, of which 58 underwent LLIF at L4-L5 and 64 underwent LLIF between L1 and L4. There were no visceral or vascular injuries or lumbar plexus injuries in either cohort. There was no significant difference in the rate of postoperative hip pain, anterior thigh dysesthesias, and/or hip flexor weakness between the cohorts (53.5% L4-L5 vs. 37.5% L1-L4; P =0.102). All patients reported complete resolution of these symptoms by 6-month postoperative follow-up. DISCUSSION: LLIF surgery at the L4-L5 level is associated with a similar infrequent likelihood of approach-related complications and postoperative hip pain, thigh dysesthesias, and hip flexor weakness when compared with upper lumbar level LLIF. Careful patient selection, meticulous use of real-time neuromonitoring, and an understanding of the anatomic location of the lumbar plexus to the working corridor are critical to success.

Reasons for revision following stand-alone anterior lumbar interbody fusion and lateral lumbar interbody fusion.

OBJECTIVE: Anterior lumbar interbody fusion (ALIF) and lateral lumbar interbody fusion (LLIF) are alternative and less invasive techniques to stabilize the spine and indirectly decompress the neural elements compared with open posterior approaches. While reoperation rates have been described for open posterior lumbar surgery, there are sparse data on reoperation rates following these less invasive procedures without direct posterior decompression. This study aimed to evaluate the overall rate, cause, and timing of reoperation procedures following anterior or lateral lumbar interbody fusions without direct posterior decompression. METHODS: This was a retrospective cohort study of all consecutive patients indicated for an ALIF or LLIF for lumbar spine at a single academic institution. Patients who underwent concomitant posterior fusion or direct decompression surgeries were excluded. Rates, causes, and timing of reoperations were analyzed. Patients who underwent a revision decompression were matched with patients who did not require a reoperation, and preoperative imaging characteristics were analyzed to assess for risk factors for the reoperation. RESULTS: The study cohort consisted of 529 patients with an average follow-up of 2.37 years; 40.3% (213/529) and 67.3% (356/529) of patients had a minimum of 2 years and 1 year of follow-up, respectively. The total revision rate was 5.7% (30/529), with same-level revision in 3.8% (20/529) and adjacent-level revision in 1.9% (10/529) of patients. Same-level revision patients had significantly shorter time to revision (7.14 months) than adjacent-level revision patients (31.91 months) (p < 0.0001). Fifty percent of same-level revisions were for a posterior decompression. After further analysis of decompression revisions, an increased preoperative canal area was significantly associated with a lower risk of further decompression revision compared to the control group (p = 0.015; OR 0.977, 95% CI 0.959-0.995). CONCLUSIONS: There was a low reoperation rate after anterior or lateral lumbar interbody fusions without direct posterior decompression. The majority of same-level reoperations were due to a need for further decompression. Smaller preoperative canal diameters were associated with the need for revision decompression.

Cervical Spine Endplate Abnormalities and Association With Pain, Disability, and Adjacent Segment Degeneration After Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: A retrospective study with prospectively-collected data. OBJECTIVE: To determine how type, location, and size of endplate lesions on magnetic resonance imaging (MRI) may be associated with symptoms and clinical outcomes after anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Structural endplate abnormalities are important, yet understudied, phenomena in the cervical spine. ACDF is a common surgical treatment for degenerative disc disease; however, adjacent segment degeneration/disease (ASD) may develop. METHODS: Assessed the imaging, symptoms and clinical outcomes of 861 patients who underwent ACDF at a single center. MRI and plain radiographs of the cervical spine were evaluated. Endplate abnormalities on MRI were identified and stratified by type (atypical, typical), location, relation to operative levels, presence at the adjacent level, and size. These strata were assessed for association with presenting symptoms, patient-reported, and postoperative outcomes. RESULTS: Of 861 patients (mean follow-up: 17.4 months), 57.3% had evidence of endplate abnormalities, 39.0% had typical abnormalities, while 18.2% had atypical abnormalities. Patients with any endplate abnormality had greater odds of myelopathy irrespective of location or size, while sensory deficits were associated with atypical lesions (P = 0.016). Typical and atypical abnormalities demonstrated differences in patient-reported outcomes based on location relative to the fused segment. Typical variants were not associated with adverse surgical outcomes, while atypical lesions were associated with ASD (irrespective of size/location; P = 0.004) and reoperations, when a large abnormality was present at the proximal adjacent level (P = 0.025). CONCLUSION: This is the first study to examine endplate abnormalities on MRI of the cervical spine, demonstrating distinct risk profiles for symptoms, patient-reported, and surgical outcomes after ACDF. Patients with typical lesions reported worsening postoperative pain/disability, while those with atypical abnormalities experienced greater rates of ASD and reoperation. This highlights the relevance of a degenerative spine phenotypic assessment, and suggests endplate abnormalities may prognosticate clinical outcomes after surgery. LEVEL OF EVIDENCE: 3.

Pediatric cellular neurothekeoma: Seven cases and systematic review of the literature.

BACKGROUND/OBJECTIVES: Neurothekeoma is a rare, benign, cutaneous neoplasm consisting of Schwann cells and perineural cells in myxoid stroma. Cellular neurothekeoma (CNT) was previously thought to represent a morphologic variant of neurothekeoma, but recent studies have shown that CNTs are unrelated to neurothekeomas and are more likely of histiocytic lineage. METHODS: Herein, we describe seven cases of CNT in pediatric patients. A comprehensive search of PubMed was performed, and 71 cases of cellular neurothekeoma in pediatric patients were reviewed. RESULTS: The clinical differential diagnosis for these lesions included Spitz nevi, keloid, juvenile xanthogranuloma, cutaneous lymphoid hyperplasia, and lymphomatoid papulosis. All cases were treated by excision or excisional biopsy. Histopathologically, all demonstrated multilobular, primarily intradermal neoplasms composed of plump spindled or epithelioid mononuclear cells with abundant eosinophilic pale-staining cytoplasm. Immunophenotypic findings included CD68 and NKI/C3 positivity, and negative staining with cytokeratin, S-100, Melan-A, and SOX-10. CONCLUSION: Cellular neurothekeoma is distinguished from conventional neurothekeoma by increased cellularity, a lack of myxoid stroma, and a lack of neural expression with immunohistochemical stains. These uncommon neoplasms should be included in the differential diagnosis of dermal nodules in children. Accurate diagnosis of these lesions is essential, as they can be mistaken for malignancy leading to unnecessary treatment.

neoepiscope improves neoepitope prediction with multivariant phasing.

MOTIVATION: The vast majority of tools for neoepitope prediction from DNA sequencing of complementary tumor and normal patient samples do not consider germline context or the potential for the co-occurrence of two or more somatic variants on the same mRNA transcript. Without consideration of these phenomena, existing approaches are likely to produce both false-positive and false-negative results, resulting in an inaccurate and incomplete picture of the cancer neoepitope landscape. We developed neoepiscope chiefly to address this issue for single nucleotide variants (SNVs) and insertions/deletions (indels). RESULTS: Herein, we illustrate how germline and somatic variant phasing affects neoepitope prediction across multiple datasets. We estimate that up to ∼5% of neoepitopes arising from SNVs and indels may require variant phasing for their accurate assessment. neoepiscope is performant, flexible and supports several major histocompatibility complex binding affinity prediction tools. AVAILABILITY AND IMPLEMENTATION: neoepiscope is available on GitHub at https://github.com/pdxgx/neoepiscope under the MIT license. Scripts for reproducing results described in the text are available at https://github.com/pdxgx/neoepiscope-paper under the MIT license. Additional data from this study, including summaries of variant phasing incidence and benchmarking wallclock times, are available in Supplementary Files 1, 2 and 3. Supplementary File 1 contains Supplementary Table 1, Supplementary Figures 1 and 2, and descriptions of Supplementary Tables 2-8. Supplementary File 2 contains Supplementary Tables 2-6 and 8. Supplementary File 3 contains Supplementary Table 7. Raw sequencing data used for the analyses in this manuscript are available from the Sequence Read Archive under accessions PRJNA278450, PRJNA312948, PRJNA307199, PRJNA343789, PRJNA357321, PRJNA293912, PRJNA369259, PRJNA305077, PRJNA306070, PRJNA82745 and PRJNA324705; from the European Genome-phenome Archive under accessions EGAD00001004352 and EGAD00001002731; and by direct request to the authors. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Population-level distribution and putative immunogenicity of cancer neoepitopes.

BACKGROUND: Tumor neoantigens are drivers of cancer immunotherapy response; however, current prediction tools produce many candidates requiring further prioritization. Additional filtration criteria and population-level understanding may assist with prioritization. Herein, we show neoepitope immunogenicity is related to measures of peptide novelty and report population-level behavior of these and other metrics. METHODS: We propose four peptide novelty metrics to refine predicted neoantigenicity: tumor vs. paired normal peptide binding affinity difference, tumor vs. paired normal peptide sequence similarity, tumor vs. closest human peptide sequence similarity, and tumor vs. closest microbial peptide sequence similarity. We apply these metrics to neoepitopes predicted from somatic missense mutations in The Cancer Genome Atlas (TCGA) and a cohort of melanoma patients, and to a group of peptides with neoepitope-specific immune response data using an extension of pVAC-Seq (Hundal et al., pVAC-Seq: a genome-guided in silico approach to identifying tumor neoantigens. Genome Med 8:11, 2016). RESULTS: We show neoepitope burden varies across TCGA diseases and HLA alleles, with surprisingly low repetition of neoepitope sequences across patients or neoepitope preferences among sets of HLA alleles. Only 20.3% of predicted neoepitopes across TCGA patients displayed novel binding change based on our binding affinity difference criteria. Similarity of amino acid sequence was typically high between paired tumor-normal epitopes, but in 24.6% of cases, neoepitopes were more similar to other human peptides, or bacterial (56.8% of cases) or viral peptides (15.5% of cases), than their paired normal counterparts. Applied to peptides with neoepitope-specific immune response, a linear model incorporating neoepitope binding affinity, protein sequence similarity between neoepitopes and their closest viral peptides, and paired binding affinity difference was able to predict immunogenicity (AUROC = 0.66). CONCLUSIONS: Our proposed prioritization criteria emphasize neoepitope novelty and refine patient neoepitope predictions for focus on biologically meaningful candidate neoantigens. We have demonstrated that neoepitopes should be considered not only with respect to their paired normal epitope, but to the entire human proteome, and bacterial and viral peptides, with potential implications for neoepitope immunogenicity and personalized vaccines for cancer treatment. We conclude that putative neoantigens are highly variable across individuals as a function of cancer genetics and personalized HLA repertoire, while the overall behavior of filtration criteria reflects predictable patterns.

Clinical Features and Treatment of Fibrous Histiocytomas of the Tongue: A Systematic Review.

Introduction Benign fibrous histiocytomas are common lesions of the skin that rarely affect the tongue. Such cases are available in the literature exclusively as case reports. Similarly, malignant fibrous histiocytoma, now classified as undifferentiated pleomorphic sarcoma, is exceedingly rare in the tongue and not fully understood. Objectives This study systematically reviews the available literature discussing the clinical and pathological features of malignant and benign fibrous histiocytomas. Data Synthesis A total of 20 cases were included in this review. Patient-level data were extracted from cases to include clinical presentation, workup, treatment, and outcome. Conclusion Benign fibrous histiocytomas are consistent in clinical and histopathologic presentation. Surgical treatment provides excellent outcome, with no recurrence in all excised cases. Malignant tumors have a more aggressive clinical and pathological presentation. Surgical treatment with possible adjuvant radiotherapy resulted in recurrence in 40% of cases (follow-up of 24 months), and death due to disease in 47% of patients (follow-up of 19 months).

Clinical Features and Treatment of Fibrous Histiocytomas of the Tongue: A Systematic Review

Abstract Introduction Benign fibrous histiocytomas are common lesions of the skin that rarely affect the tongue. Such cases are available in the literature exclusively as case reports. Similarly, malignant fibrous histiocytoma, now classified as undifferentiated pleomorphic sarcoma, is exceedingly rare in the tongue and not fully understood. Objectives This study systematically reviews the available literature discussing the clinical and pathological features of malignant and benign fibrous histiocytomas. Data Synthesis A total of 20 cases were included in this review. Patient-level data were extracted from cases to include clinical presentation, workup, treatment, and outcome. Conclusion Benign fibrous histiocytomas are consistent in clinical and histopathologic presentation. Surgical treatment provides excellent outcome, with no recurrence in all excised cases. Malignant tumors have a more aggressive clinical and pathological presentation. Surgical treatment with possible adjuvant radiotherapy resulted in recurrence in 40% of cases (follow-up of 24 months), and death due to disease in 47% of patients (follow-up of 19 months).

Clinical Features and Surgical Treatment of Schwannoma Affecting the Base of the Tongue: A Systematic Review.

Introduction Schwannomas of the head and neck account for 25-40% of all cases, with presentation at the base of the tongue as the most frequent site for intraoral tumors. Objectives Here, a systematic review was conducted to include 15 cases of patients with schwannoma of the base of the tongue. Data Synthesis Most patients presented with a single, painless, well-encapsulated nodule at the base of the tongue. These nodules were slow-growing, with an average of 13.3 months from onset to presentation. Most cases were accompanied by airway obstruction, indicated by symptoms of dysphagia, dysarthria, snoring, and sleep apnea. Overall, the histological studies were consistent with a benign schwannoma with a palisading Antoni A and Antoni B pattern without malignant changes in cell morphology. These tumors were treated via complete surgical excision, and all cases achieved full remission by final follow-up. Conclusion Surgical removal is the primary mode of treatment with excellent postoperative prognosis and rare instances of recurrence. Given the rarity of this tumor, this review of available case studies serves to comprehensively describe clinical presentation and surgical treatment approaches to tongue base schwannoma.

Group B streptococcus (GBS) is an important pathogen in human disease- but what about in cystic fibrosis?

BACKGROUND: Group B Streptococcus (GBS) is a common commensal capable of causing severe invasive infections. Most GBS infections occur in neonates (often as pneumonia). GBS can also cause infection in adults with diabetes and other immunological impairments but rarely leads to pneumonia in adults. GBS has occasionally been found in the sputum of Cystic Fibrosis (CF) patients, an inherited condition known for progressive lung disease. However, the epidemiology and clinical significance of GBS in CF are not understood. METHODS: We retrospectively reviewed a large single-centre adult CF population with an associated comprehensive, prospectively collected bacterial biobank beginning in 1978. We identified all individuals with GBS isolated from their sputum on at least one occasion. The primary outcome was risk of pulmonary exacerbation (PEx) at the time of the first GBS isolate compared to the preceding visit. Secondary outcomes included determining: prevalence of GBS infection in a CF population, whether GBS infections where transient or persistent, whether GBS strains were shared among patients, change in % predicted FEV1 at the time of GBS isolate compared to the preceding visit, PEx frequency after the first GBS isolate, change in % predicted FEV1 after the first GBS isolate, and complications of GBS infection. RESULTS: GBS was uncommon, infecting 3.5% (11/318) adults within our cohort. Only three individuals developed persistent GBS infection, all lasting > 12 months. There were no shared GBS strains among patients. PEx risk was not increased at initial GBS isolation (RR 5.0, CI 0.69-36.1, p=0.10). In the two years preceding initial GBS isolation compared to the two following years, there was no difference in PEx frequency (median 2, range 0-4 vs 1, range 0 to 5, respectively, p=0.42) or lung function decline, as measured by % predicted FEV1, (median -1.0%, range -19 to 7% vs median -6.0%, range -18 to 22%, p=0.86). There were no invasive GBS infections. CONCLUSION: In adults with CF, GBS is uncommon and is generally a transient colonizer of the lower airways. Despite the presence of structural lung disease and impaired innate immunity in CF, incident GBS infection did not increase PEx risk, PEx frequency, rate of lung function decline, or other adverse clinical outcomes.

Clinical Features and Surgical Treatment of Schwannoma Affecting the Base of the Tongue: A Systematic Review

Abstract Introduction Schwannomas of the head and neck account for 25-40% of all cases, with presentation at the base of the tongue as the most frequent site for intraoral tumors. Objectives Here, a systematic review was conducted to include 15 cases of patients with schwannoma of the base of the tongue. Data Synthesis Most patients presented with a single, painless, well-encapsulated nodule at the base of the tongue. These nodules were slow-growing, with an average of 13.3 months from onset to presentation. Most cases were accompanied by airway obstruction, indicated by symptoms of dysphagia, dysarthria, snoring, and sleep apnea. Overall, the histological studies were consistent with a benign schwannoma with a palisading Antoni A and Antoni B pattern without malignant changes in cell morphology. These tumors were treated via complete surgical excision, and all cases achieved full remission by final follow-up. Conclusion Surgical removal is the primary mode of treatment with excellent postoperative prognosis and rare instances of recurrence. Given the rarity of this tumor, this review of available case studies serves to comprehensively describe clinical presentation and surgical treatment approaches to tongue base schwannoma.

Clinical Implications of Augmenter of Liver Regeneration in Cancer: A Systematic Review.

BACKGROUND/AIM: Hepatocellular carcinoma is a substantial healthcare burden with high prevalence and poor prognosis. As such, efforts are continually made to uncover molecules relevant in cancer biology, that are exploitable as targets for therapy. The mitochondrion is the powerhouse of the cell and exhibits altered functionality in the malignant state, including aberrant regulation of apoptosis and cellular respiration. Augmenter of liver regeneration (ALR) is a multifunctional mitochondrial protein that demonstrates anti-oxidative and anti-apoptotic properties and plays a key role in liver regeneration. MATERIALS AND METHODS: The present study systematically reviews the available literature on the role of ALR in cancer. RESULTS: Systematic search of PubMed resulted in 12 studies discussing ALR in multiple types of cancer. More specifically, ALR appears to be up-regulated in malignant cells and tissues. Furthermore, treatment of cells with exogenous ALR shows an anti-apoptotic effect while silencing or inhibiting ALR decreases cell and tumor survival. CONCLUSION: ALR clearly plays a role in cancer biology and demonstrates potential as a therapeutic target.

Comparison of 3 Different Perioperative Care Models for Patients With Hip Fractures Within 1 Health Service.

INTRODUCTION: Orthogeriatric care models have been introduced within many health-care facilities to improve outcomes for hip fracture patients. This study aims to evaluate differences in care between 3 models, an orthopedic model, a geriatric model, and a comanaged model. MATERIALS AND METHODS: A retrospective analysis was conducted for hip fracture patients treated at Western Health between November 2012 and March 2014. All patients aged 65 years or older were included in the analysis. RESULTS: There were 183 patients in the orthopedic model, 137 in the geriatric model, and 126 in the comanaged model. Demographics and clinical characteristics were similar across the 3 models. Length of stay, mortality, and discharge destination were also consistent across the 3 groups. However, groups involving geriatricians were more likely to receive preoperative medical assessments, have greater recognition of postoperative medical problems, and have implementation of long-term osteoporosis management. CONCLUSION: The involvement of geriatricians in perioperative care models resulted in more comprehensive medical care without impacting length of stay, mortality, or discharge destination.

Clinical Features and Treatment of Dermatofibrosarcoma Protuberans Affecting the Vulva: A Literature Review.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a low-to-intermediate grade cutaneous neoplasm with a low propensity for metastasis and a high rate of local recurrence. It typically presents as a dermal plaque or nodule on the trunk, limbs, or head and neck region. Vulvar DFSP has also been described, although it is less common. OBJECTIVE: To review the available literature and discuss the clinical course of DFSP affecting the vulva. MATERIALS AND METHODS: We reviewed the existing English-language literature on DFSP of the vulva with respect to clinical presentation, diagnosis, treatment, and outcome. RESULTS: Thirty three case reports and series were included (n = 54 patients). Vulvar DFSP most commonly presents as a slowly enlarging tender or asymptomatic mass on the labia majora, with histological findings of classic DFSP. Most patients were treated with wide local excision. Three patients were treated with Mohs micrographic surgery, which may decrease local recurrence and seems well suited for use in vulvar DFSP. CONCLUSION: This literature review comprehensively reviews and describes the clinical presentation of vulvar DFSP and the treatment options for this rare vulvar neoplasm.