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In Australia, three to five children die each year because of otitis media complications, and 15 children will suffer permanent hearing loss each year as a result of otitis media. Extracranial complications occur most commonly, and include mastoiditis, cholesteatoma and otitis media with perforation. Intracranial complications are less common, and include meningitis, brain abscess and lateral sinus thrombosis. In Australia, approximately 60% of extracranial and intracranial complications of otitis media occur in children. The contrasting rates of childhood otitis media among Indigenous and non-Indigenous children have implications for the frequency and types of complications occurring in both groups. Otitis media with effusion and acute otitis media predominate among non-Indigenous children, whereas chronic suppurative otitis media (CSOM) occurs most commonly among Indigenous children. The incidence of mastoiditis in Australia is low by international standards (2/100,000 children), but cholesteatoma rates among Indigenous children in Australia are higher than previously estimated (up to 10% in CSOM). A high rate of chronic tympanic membrane perforation occurs among Indigenous children, estimated to be as high as 80%. Intracranial complications of otitis media are uncommon, but are potentially life-threatening and are more likely to occur among Indigenous than non-Indigenous children. Reduced access to medical care, lower socioeconomic status and remote living conditions mean that levels of early childhood hearing loss among Indigenous children are likely to be underestimated. This has implications for early childhood speech and language development and education. [ABSTRACT FROM AUTHOR]

Algal blooms of Karenia brevis produce brevetoxins that lead to the natural phenomenon of red tide. Beyond monitoring the red tide concentration and forecasting future outbreaks, uncertainty exists in the field when examining these toxins in relation to physiologic aspect of humans. Contaminated air that results from outbreaks of K. brevis leads to inhalation of aerosolized brevetoxins, which directly impact the human respiratory system. This scoping review focused on the respiratory effects of red tide and was conducted by using a comparative method between 2 researchers. Relevant abstracts were collected, and full-text articles were reviewed by using PubMed, Science Direct, CINAHL Complete, and BioMed Central databases. Thirty articles were included in the final analysis and categorized by study design, location, and number and age of participants, and were also divided into assessment by respiratory effects, exposure, measurements of K. brevis, and asthma. The research indicates that respiratory health issues exist and can be compounded with exposure to red tide, specifically upper respiratory symptoms. Both symptomatic issues and pulmonary function tests were of concern when individuals were subjected to brevetoxin exposure. Even low levels of K. brevis resulted in negative respiratory health effects. Red tide is common in many areas of the world. The toxins released can cause adverse respiratory effects in humans. This article provides a comprehensive summary of the scholarly literature focused on the respiratory system and red tide produced by K. brevis ., (Copyright © 2024 by Daedalus Enterprises.)

Purpose: On the basis of the results of the ZUMA-3 trial, brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, gained US Food and Drug Administration approval in October 2021 for adults with relapsed/refractory (R/R) B-cell ALL (B-ALL). We report outcomes of patients treated with brexu-cel as a standard therapy., Methods: We developed a collaboration across 31 US centers to study adults with B-ALL who received brexu-cel outside the context of a clinical trial. Data were collected retrospectively from October 2021 to October 2023. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)., Results: At the time of data lock, 204 patients had undergone apheresis and 189 were infused. Median follow-up time was 11.4 months. Forty-two percent of patients received brexu-cel in morphologic remission and would have been ineligible for participation in ZUMA-3. After brexu-cel, 151 achieved complete remission (CR), of which 79% were measurable residual disease (MRD) negative remissions. Median progression-free survival (PFS) was 9.5 months and median overall survival was not reached. Grade 3-4 CRS or ICANS occurred in 11% and 31%, respectively. In multivariable analysis, patients receiving consolidative hematopoietic cell transplantation (HCT; hazard ratio, 0.34 [95% CI, 0.14 to 0.85]) after brexu-cel had superior PFS compared with those who did not receive any consolidation or maintenance therapy., Conclusion: Similar to ZUMA-3, high rates of MRD-negative CR were observed after brexu-cel treatment for R/R B-ALL. The use of HCT as consolidation after brexu-cel resulted in improved PFS.

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL), particularly the influence off previous InO response and the timing of administration. We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory (r/r) ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO-exposed). InO-exposed patients were more heavily pretreated (p= 0.02) and frequently had active marrow disease pre-apheresis (p= 0.03). Response rate and toxicity profile following brexu-cel were comparable for InO-exposed and InO-naïve; however, consolidation therapy post brexu-cel response was utilized at a higher rate in InO-naïve patients (p= 0.005). With a median follow up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS) (p=0.013) and overall survival (OS) (p=0.006) in univariate analyses; however, prior InO exposure did not influence PFS (HR 1.20, 95%CI, 0.71-2.03) in multivariate models. When InO-exposed patients were stratified according to prior InO response, InO responders had superior PFS (p=0.002) and OS (p<0.0001) relative to InO-refractory. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (p=0.51) and OS (p=0.86) for patients receiving InO as bridging therapy or pre-apheresis. In conclusion, while InO exposure was associated with inferior survival outcomes following brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively impacts brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology., (Copyright © 2024 American Society of Hematology.)

Background: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes., Methods: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O 2 , hospitalized and received supplemental O 2 , admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality., Results: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity., Conclusions: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19., (© 2024 American Cancer Society.)

Objective: Proximal junctional failure following surgical correction for adult spinal deformity significantly impacts quality of life and increases the economic burden of treating underlying spinal deformity. The objective of this cadaver study was to determine optimal tension parameters in junctional tethers for proximal junctional kyphosis prevention., Methods: Cadaveric specimens were used to establish the optimal tension range in polyethylene tethering devices, such as the VersaTie (NuVasive) used in this study. Three specimens were instrumented to test tether tensions of 0, 75, and 150 Newtons (N) at L1-L2, T9-T10, and T3-T4. An optical tracking system was used to measure when specimens reached proximal junctional kyphosis, experienced instrumentation or tissue failure, or reached a cap of 2500 cycles. Radiographs were obtained before and after testing., Results: At all levels, use of a tether at tension forces of 75 N and 150 N elicited a protective effect. The only level in which a higher tension on the tether resulted in more protection was at T3-T4. When averaged, the use of a tether at tension forces of 75 N and 150 N showed 1000 cycles of protection at L1-L2, 2000 cycles at T9-T10, and 1426 cycles at T3-T4. Radiographic analysis corroborated these findings., Conclusions: The use of a tether in a cadaveric model prevents the development of proximal junctional kyphosis across all tested levels and an increased tension force of 150 N is protective at the proximal thoracic spine. These data can be used to develop further models for a tether system that reproducibly applies a fixed tension force above the thoracolumbar rod construct., (Copyright © 2023. Published by Elsevier Inc.)

The cervical spine poses many complex challenges that require complex solutions. Anterior cervical discectomy and fusion (ACDF) has been one such technique often employed to address such issues. In order to address the problems with ACDF and assess the modifications that have been made to the technique over time, finite element analyses (FEA) have proven to be an effective tool. The variations of cervical spine FEA models that have been produced over the past couple of decades, particularly more recent representations of more complex geometries, have not yet been identified and characterized in any literature. Our objective was to present material property models and cervical spine models for various simulation purposes. The outlining and refinement of the FEA process will yield more reliable outcomes and provide a stable basis for the modeling protocols of the cervical spine.

Study Design: Cadaver study., Objectives: Assess the feasibility of robot-assisted cervical pedicle screw (RA-CPS) placement and understand the anatomical considerations of this technique., Methods: Four cadaver specimens free from bony pathology were acquired. Anatomical considerations, such as pedicle width (PW) and height (PH), transverse pedicle angle (TPA), and maximal screw length (MSL), were recorded from preoperative computational tomography (CT) scans. Intraoperative cone-beam CT was acquired and registered to the robotic system. After cervical levels were segmented, screw sizes and trajectories were planned, and RA-CPS were placed. Accuracy was assessed using Gertzbein and Robbin's classification on postoperative CT scans., Results: Thirty-five RA-CPS were placed. Major breaches (≥Grade C) occurred in 28.57% screws. Grade A or B accuracy was found in 71.43% of screws, with the most common direction of breach being medial (81.3%). The greatest proportion of breach per level occurred in the upper subaxial levels, (C3:71.4%, C4 66.6%, C5:50%) which had the smallest PW (C3: 4.34 ± .96 mm, C4: 4.48 ± .60, C5: 5.76 ± 1.11). PH was greatest at C2 (8.14 ± 1.89 mm) and ranged subaxial from 6.36 mm (C3) to 7.48 mm (C7). The mean PW was 5.37 mm and increased caudally from 4.34 mm (C3) to 6.31 mm (C7). The mean TPA was 39.9° and decreased moving caudally 46.9°) to C7 (34.4°). The MSL was 37.1 mm and increased from C2 (26.3 mm) to C7 (41.0 mm)., Conclusion: RA-CPS has the potential to be feasible, but technological and instrument modifications are necessary to increase the accuracy in the cervical region.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited., Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF., Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated., Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p <0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], p interaction <0.001)., Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)., Competing Interests: R.M reports research funding from Bayer, Pfizer, and Tempus; and 18 personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, 19 Caris, Dendreon, Exelixis, Janssen, Johnson and Johnson, Merck & Co, Myovant, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, Tempus, and Vividion. A.N. reports consulting fees from AstraZeneca, Takeda Oncology and Bantam Pharmaceuticals. B.B. reports research support to institution from Amgen, Bicycle Therapeutics, Boehringer Ingelheim, Ikena Oncology, Kahr Medical, Merck, Syros, Tarveda Therapeutics. Z.B. receives research support from 10.13039/100004328Genentech/imCORE and Bristol Myers Squibb. Personal fees from UpToDate. L.A.F reports clinical trial funding from BMS, EMDserono, Pfizer, Merck, Array, Kartos, Incyte, personal fees from Elsevier, ViaOncology, outside the submitted work. J.L.W. reports research funding from NIH/NCI during the conduct of the work, research funding from AACR, consulting fees from Westat, Roche, Flatiron Health, Melax Tech, other from HemOnc.org LLC (ownership), outside the submitted work. C.H reports stock holdings in Johnson and Johnson; research funding to institution from Merck, Bausch Health, Genentech, Bayer, and AstraZeneca, consultant fees from Tempus, Genzyme, and EMD Sorono, speaking fees from OncLive/MJH Life Sciences, travel fees from Merck, all outside the submitted work. The remaining authors have nothing to disclose., (© 2023 Published by Elsevier Inc.)

Objective: This study aimed to assess the risk of maintenance immunosuppression on the post-transplant risk of malignancy across all solid organ transplant types., Methods: This is a retrospective cohort study from a multicenter hospital system in the United States. The electronic health record was queried from 2000 to 2021 for cases of solid organ transplant, immunosuppressive medications, and post-transplant malignancy., Results: A total of 5,591 patients, 6,142 transplanted organs, and 517 post-transplant malignancies were identified. Skin cancer was the most common type of malignancy at 52.8%, whereas liver cancer was the first malignancy to present at a median time of 351 days post-transplant. Heart and lung transplant recipients had the highest rate of malignancy, but this finding was not significant upon adjusting for immunosuppressive medications (heart HR 0.96, 95% CI 0.72 - 1.3, p = 0.88; lung HR 1.01, 95% CI 0.77 - 1.33, p = 0.94). Random forest variable importance calculations and time-dependent multivariate cox proportional hazard analysis identified an increased risk of cancer in patients receiving immunosuppressive therapy with sirolimus (HR 1.41, 95% CI 1.05 - 1.9, p = 0.04), azathioprine (HR 2.1, 95% CI 1.58 - 2.79, p < 0.001), and cyclosporine (HR 1.59, 95% CI 1.17 - 2.17, p = 0.007), while tacrolimus (HR 0.59, 95% CI 0.44 - 0.81, p < 0.001) was associated with low rates of post-transplant neoplasia., Conclusion: Our results show varying risks of immunosuppressive medications associated with the development of post-transplant malignancy, demonstrating the importance of cancer detection and surveillance strategies in solid organ transplant recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shaw, Haque, Luu, O’Connor, Hamidi, Fitzsimons, Varda, Kwon, Whitcomb, Gregorowicz, Roloff, Bemiss, Kallwitz, Hagen and Berg.)

Hereditary hematopoietic malignancies (HHMs) are inherited syndromes that confer the risk of blood cancer development. With the rapid acceleration of next-generation sequencing (NGS) into commercial biotechnology markets, HHMs are increasingly recognized by genetic counselors and clinicians. In 2020, it was demonstrated that most diagnostic test offerings for HHMs were insufficient for accurate diagnosis, failing to sequence the full spectrum of genetic events known to cause HHMs. We hypothesized the number of genes on commercially available HHM assay increased from 2020 to 2022, consistent with a more comprehensive sequencing approach. Here, we analyzed assays from eight commercial laboratories to determine the HHM-related genes sequenced by these assays. We compared these assays with panels from 2020 to determine trends in sequencing quality. Most HHM diagnostic assays did not change and remain insensitive for the detection of all HHM-related variants. Most (75%) HHM assays do not sequence CHEK2, the gene most frequently mutated in HHMs, and 25% of HHM assays does not sequence DDX41, the second most frequent HHM driver. The quality of HHM diagnostic assays stagnated despite the discovery of novel HHM-related genes and prior work demonstrating heterogeneity in the quality of HHM testing. Most commercially available HHM tests remain insufficient., (© 2023 National Society of Genetic Counselors.)

In recent years, advances in genetics and the integration of clinical-grade next-generation sequencing (NGS) assays into patient care have facilitated broader recognition of hereditary hematopoietic malignancy (HHM) among clinicians, in addition to the identification and characterization of novel HHM syndromes. Studies on genetic risk distribution within affected families and unique considerations of HHM biology represent exciting areas of translational research. More recently, data are now emerging pertaining to unique aspects of clinical management of malignancies arising in the context of pathogenic germline mutations, with particular emphasis on chemotherapy responsiveness. In this article, we explore considerations surrounding allogeneic transplantation in the context of HHMs. We review pre- and post-transplant patient implications, including genetic testing donor selection and donor-derived malignancies. Additionally, we consider the limited data that exist regarding the use of transplantation in HHMs and safeguards that might be pursued to mitigate transplant-related toxicities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 O’Connor, Shaw, Madero-Marroquin and Roloff.)

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines., Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV)., Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44)., Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer., Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH)., Competing Interests: TKC reports grants, personal fees and non-financial support from Merck, BMS, Exelixis, Astra Zeneca, Eli Lilly, Eisai, Novartis, GSK, Pfizer, EMD Serono; stocks in Pionyr, Tempest, outside the submitted work; In addition, TKC reports patent: pending International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response,” filed January 3, 2018, claiming priority to U.S. Provisional Patent Application No. 62/445,094, filed January 11, 2017; pending International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy,” filed October 31, 2018, claiming priority to U.S. Provisional Patent Application No. 62/581,175, filed November 3, 2017; TKC sits on National Comprehensive Cancer Network kidney panel. CL reports grants from Genentech/ImCore. ZB reports non-financial support from Bristol Myers Squibb, grants from Genentech/ImCore, personal fees from UpToDate, outside the submitted work. ALS reports non-financial support from Astellas and Pfizer outside the submitted work. GdLL reports personal fees from Boehringer Ingelheim, Pfizer, AstraZeneca; grants from AstraZeneca, Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, Novartis, G1 Therapeutics, Adaptimmune, BMS, GSK, Abbvie, Rgenix, Pfizer, Roche, Genentech, Eli Lilly, Janssen; personal fees from Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, Janssen; all outside the submitted work. CH reports grants from Merck, Bayer, Genentech, AstraZeneca, Bausch Health; Consulting fees from Tempus, Genzyme, EMD Sorono, payment or honoraria from OncLive/MJH Life Sciences, support for attending meetings and/or travel from Merck, participation on a data safety monitoring or advisory board of Henry Ford Cancer Institute, Hoosier Cancer Research Network; Leadership or fiduciary role in Wayne County Medical Society of Southeast Michigan; Stock or stock options in Johnson and Johnson, all outside the submitted work. EAG reports Consulting fees from Alexion Inc, Picnic Health, AbbVie, CTI Biopharma, Genentech Inc., Novartis, Celgene/Bristol Myers-Squibb, Takeda oncology, Taiho Oncology and Research Funding from Genentech Inc, Astex Pharmaceuticals, and BluePrint Medicines, outside the submitted work. SH reports grants/research supports from ASCO TAPUR, Astellas; honoraria or consultation fees from Sanofi, Aveo Oncology, outside the submitted work. SB reports Consulting fees from BMS, Exelexis, Eisai, Pfizer, Myovant, SeaGen; Payment or honoraria from Exelexis, Eisai, BMS; Participation on a Data Safety Monitoring Board or Advisory Board from SeaGen, Pfizer, Myovant; Stock or stock options in Natera; outside the submitted work. MJ reports grants from AstraZeneca, Pfizer; Eisai, personal fees from Seagen, Sanofi, outside the submitted work. NTNG reports personal fees from Novocure, outside the submitted work. RRM reports Advisory board/consultant—Aveo, AstraZeneca, Bayer, Bristol Myers Squib, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novartis, Pfizer, Sanofi, Sorrento therapeutics, Pfizer, Tempus, Vividion, unrelated to this work. SMR reports advisory for Roche, Janssen, Sanofi, and EUSA Pharma, unrelated to this work. PV reports institutional research funding from Sanofi; stocks or stock options in Novavax, Biontech. HAZ acknowledges support from Georgia NCORP. CRF reports grants from Merck Foundation, grants from NCCN/Pfizer, grants from National Cancer Institute, other from National Cancer Institute, other from Patient-Centered Outcomes Research Institute, outside the submitted work. SM reports support from National Cancer Institute, and Intl Assoc. for the Study of Lung Cancer during the conduct of the study; and personal fees from National Geographic outside the submitted work. DF reports Grants or contracts from Merck, Viracor, Astellas; Support for attending meetings and/or travel from Viracor; outside the submitted work. JLW reports grants from NIH during the conduct of the study; personal fees from Roche, Westat, Flatiron Health, Melax Tech, IBM Watson Health, ownership of HemOnc.org LLC, grants from AACR; outside the submitted work. TMW-D reports grants from BMS, Merck & Co, GSK/Tesaro, Janssen; personal fees from Exicure, Shattuck Labs, SITC, Merck & Co, Caris Life Sciences, outside the submitted work. C-YH, SRKS, CJ, LBW, UW, TEO'C, OAP, EJK, HS, RN, TKN, RQ, MP, BHM, SADP, KR, BF, DYR, MKA, HS, DRR, YS, and SB have nothing to disclose. The content is solely the responsibility of the authors and does not necessarily represent the US Food and Drug Administration official views or policies., (© 2023 The Author(s).)

Study Design: This study compares four cervical endplate removal procedures, validated by finite element models., Purpose: To characterize the effect of biomechanical strength and increased contact area on the maximum von Mises stress, migration, and subsidence between the cancellous bone, endplate, and implanted cage., Overview of Literature: Anterior cervical discectomy and fusion (ACDF) has been widely used for treating patients with degenerative spondylosis. However, no direct correlations have been drawn that incorporate the impact of the contact area between the cage and the vertebra/endplate., Methods: Model 1 (M1) was an intact C2C6 model with a 0.5 mm endplate. In model 2 (M2), a cage was implanted after removal of the C4-C5 and C5-C6 discs with preservation of the osseous endplate. In model 3 (M3), 1 mm of the osseous endplate was removed at the upper endplate. Model 4 (M4) resembles M3, except that 3 mm of the osseous endplate was removed., Results: The range of motion (ROM) at C2C6 in the M2-M4 models was reduced by at least 9º compared to the M1 model. The von Mises stress results in the C2C3 and C3C4 interbody discs were significantly smaller in the M1 model and slightly increased in the M2-M3 and M3-M4 models. Migration and subsidence decreased from the M2-M3 model, whereas further endplate removal increased the migration and subsidence as shown in the transition from M3 to M4., Conclusions: The M3 model had the least subsidence and migration. The ROM was higher in the M3 model than the M2 and M4 models. Endplate preparation created small stress differences in the healthy intervertebral discs above the ACDF site. A 1 mm embedding depth created the best balance of mechanical strength and contact area, resulting in the most favorable stability of the construct.

Introduction There has been a surge in robot utilization in spine surgery over the past five years with the rapid development of new spine robotic platforms. This study aimed to compare a new robotic spine platform from Fusion Robotics TM  (Fusion Robotics, Helena, MT) with the widely used Mazor-X TM Stealth Edition robotic platform (Medtronic, Dublin, Ireland) in terms of workflow and lumbar pedicle screw placement accuracy. Methods A cadaver lab was conducted, which included four procedures with single-level lumbar pedicle screw placement using the Fusion Robotics TM system. These four procedures were compared to four propensity-score matched cases with single-level lumbar pedicle screw placement using the Mazor-X TM Stealth Edition. A single surgeon performed all surgeries. The cases were matched in terms of demographics (age, sex, race, BMI) and comorbidities (Charlson Comorbidity Index score). The primary outcome measure was the operative workflow efficiency (duration as measured with a stopwatch by an independent observer). The secondary outcome measures were pedicle screw accuracy and accuracy to plan. Results After propensity-score matching, there were four cases in each group with no significant between-group differences in terms of sex, race, BMI, or surgical levels; however, there were significant differences in terms of age (p=0.01) and comorbidities (p<0.001). The workflow efficiency measurement showed that the Fusion Robotics TM platform had a significantly shorter duration in terms of the system set-up time, planning to in-position time, and total procedure time (p<0.05). However, there was no significant difference between the robotic platforms in terms of creating a sterile barrier, scanning and importing images, creating a plan, screw placement, screw accuracy, and screw accuracy to plan. Conclusion Based on our findings, the Fusion Robotics TM  platform had a significantly shorter procedure workflow duration while maintaining the same accuracy as the most commonly used robotic platform (Mazor-X TM ). This is the first study to directly compare different spine surgery robotic systems., Competing Interests: Dr. Khan received a research grant from the Scoliosis Research Society to study scoliosis in Chiari patients., (Copyright © 2021, Soliman et al.)

Study Design: Retrospective review., Objective: Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure that may be complicated by airway compromise postoperatively. This life-threatening complication may necessitate reintubation and reoperation. We evaluated the cost utility of conventional postoperative x-ray., Summary of Background Data: Studies have demonstrated minimal benefit in obtaining an x-ray on postoperative day 1, but there is some utility of postanesthesia care unit (PACU) x-rays for predicting the likelihood of reoperation., Methods: We retrospectively reviewed the records of consecutive patients who underwent ACDF between September 2013 and February 2017. Patients were dichotomized into those who received PACU x-rays and those who did not (control group). Primary outcomes were reoperation, reintubation, mortality, and health care costs., Results: Eight-hundred and fifteen patients were included in our analysis: 558 had PACU x-rays; 257 did not. In those who received PACU x-rays, mean age was 53.7 ± 11.3 years, mean levels operated on were 2.0 ± 0.79, and mean body mass index (BMI) was 30.3 ± 6.9. In those who did not, mean age was 51.8 ± 10.9 years, mean levels operated on were 1.48 ± 0.65, and mean BMI was 29.9 ± 6.3. Complications in the PACU x-ray group were reintubation-0.4%, reoperation-0.7%, and death-0.3% (due to prevertebral swelling causing airway compromise). Complications in the control group were reintubation-0.4%, reoperation-0.8%, and death-0. There were no differences between groups with respect to reoperation (P = 0.92), reintubation (P = 0.94), or mortality (P = 0.49). The mean per-patient cost was significantly higher (P = 0.009) in those who received PACU x-rays, $1031.76 ± 948.67, versus those in the control group, $700.26 ± 634.48. Mean length of stay was significantly longer in those who had PACU x-rays (P = 0.01)., Conclusion: Although there were no differences in reoperation, reintubation, or mortality, there was a significantly higher cost for care and hospitalization in those who received PACU x-rays. Further studies are warranted to validate the results of the presented study.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Biopsy of pineal region neoplasms is frequently accomplished by way of endoscopic transventricular access or using an image-guided, computer-assisted stereotactic approach., Methods: We evaluated a nonorthogonal lateral temporal approach for stereotactic biopsy of pineal region tumors as a variation of previously described stereotactic methods. Magnetic resonance imaging-guided frameless stereotaxy was used to plan and perform biopsies of pineal region tumors using a nonorthogonal trajectory extending from the superior or middle temporal gyri through the temporal stem, anterior to the atrium of the lateral ventricle, and posterior to the corticospinal tract., Results: All patients had an uncomplicated postoperative course and remained at neurologic baseline. No parenchymal or ventricular hemorrhage was present on postoperative scans. A tissue diagnosis was obtained in all patients., Conclusions: This method appears to be a safe alternative to stereotactic biopsy using other trajectories and provides adequate tissue for definitive diagnosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Lumbar spine fusion surgery is traditionally performed with rigid fixation. Because the rigidity is often supraphysiologic, semirigid rods were developed. To the best of our knowledge, a comprehensive evaluation of rod material type on surgical outcomes has yet to be conducted., Methods: A systematic review based on PRISMA guidelines was conducted across 3 electronic databases. After examination for inclusion and exclusion criteria, data were extracted from the studies., Results: Seventeen studies, including 1399 patients, were included in this review. The mean rigid rod fusion rate is 92.2% and 95.5% for semirigid rods (P = 0.129). The mean improvement in back pain was 60.6% in rigid rods and 71.6% in semirigid rods. The improvement in leg pain was 81.9% and 77.2%, respectively. There were no differences in visual analog scale back pain score (P = 0.098), visual analog scale leg pain score (P = 0.136), or in functional improvement between rigid and semirigid rods (P = 0.143). There was no difference (P = 0.209) in the reoperation rate between rigid rods (13.1%) and semirigid rods (6.5%). There was a comparable incidence of adjacent segment disease (3%), screw fracture (1.7%), and wound infection (1.9%) between rod material types., Conclusions: There is a moderate level of evidence supporting that surgical intervention results in high fusion rates regardless of rod material type. Surgical intervention improves back pain, leg pain, and function, with neither material type showing clear superiority. There are comparable rates of reoperation, development of adjacent segment disease, development of mechanical complications, and incidence of infection in both rigid and semirigid rods. Further studies regarding rod material type are warranted., (Published by Elsevier Inc.)

The objective of this review was to understand the clinical utilization, utility, and variability in the usage of adjunctive hyperbaric oxygen therapy (HBOT). Surgical site infection is associated with high morbidity and mortality, increased health care expenditure, and decreased quality of life. With the increasing prevalence of adult spinal deformity and spinal fusion surgery, it is imperative to understand the potential benefits of adjunctive treatments. HBOT is a safe and common procedure indicated to treat various medical conditions. We conducted a literature search across 3 databases for English articles published between December 1, 2019 and December 1, 2000. Thirteen studies were included. HBOT may lessen the duration of antimicrobial therapy and mitigate instrument removal and revision surgery. The current usage indications for HBOT are supported by level III evidence for chronic osteomyelitis and level IV evidence for osteoradionecrosis. However, the same level of evidence exists to support the beneficial use of adjunctive HBOT for noncomplicated spinal infections within 2 months after surgery. When cultured, the most common organisms were Staphylococcus aureus and other low-virulence organisms. The most common treatment protocol consists of 90-minute sessions of 100% Fio 2 at 2-3 atmosphere absolute with a mean of 35.3 ± 11.6 sessions for 5.2 ± 1.4 weeks. Adjunctive HBOT should be considered in select high-risk patients. Further improvements in diagnosis and categorization of spinal infections are necessary and will indelibly aid the decision making for the initiation of HBOT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Minimally invasive techniques in spine surgery have continued to advance as robotic technology has evolved over several generations. Although traditional techniques for placing pedicle screws are still widespread in practice, newer technology has increased the reliability of accurately placing instrumentation with smaller incisions and subsequent decreased length of stay. Additionally, advancements in planning software have improved the ability to align posterior instrumentation to assist with rod placement on multilevel constructs., Methods: This paper describes the surgical techniques and operative workflow for placing pedicle screws with the latest robotic technology. The robotic platform, registration, surgical planning, and placement of instrumentation are discussed in detail. Advantages of the Mazor X Stealth Edition compared with the previous generation robot include obviating the need for K wires and eliminating the need for a percutaneous pin, as navigation is integrated into the robot., Results: Our use of this new technology has been encouraging. Using the techniques described in this paper, the first 90 pedicle screws placed with the Mazor X Stealth Edition robot yielded 100% grade A accuracy on the Gertzbein-Robbins scale confirmed on immediate postoperative CT. There were no complications experienced in any case., Conclusions: In our experience, this robotic technology has the potential to improve patient outcomes and is associated with advanced surgical planning compared with more traditional techniques., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cortical bone trajectories (CBTs) for pedicle screw insertion can be used to stabilize the spine. Surgeons often rely on fluoroscopy or computed tomography (CT)-navigation technologies to guide screw placement. Robotic technology has potential to increase accuracy. We report our initial experience with robotic guidance for pedicle screw insertion utilizing CBTs in patients with degenerative disc disease., Methods: A retrospective chart review was conducted using data for consecutive patients who underwent spinal stabilization using a posterior approach for CBTs. The newest robotic platform (Mazor X) was used in these cases. Accuracy was determined by applying the Ravi Scale: grade I (no breach or deviation), II (breach <2 mm), III (breach 2-4 mm), or IV (breach >4 mm). The results were compared with those for a historical cohort of patients who underwent CT navigation-guided pedicle screw insertion using CBTs., Results: Twenty-two patients underwent robot-assisted pedicle screw placement using CBTs. A total of 92 screws were inserted across 24 spinal levels with grade I accuracy and without complications in the robotic group. Eighteen patients underwent CT-navigation for CBT pedicle screw insertion. A total of 74 screws were inserted across 19 levels, 69 of which were grade I accuracy and 5 were grade II accuracy. When comparing operative time (P = 0.97), fluoroscopy time (P = 0.8), and radiation dose (P = 0.4), no significant differences were observed between cohorts., Conclusions: Robotic technology and CT-navigation technology for CBT pedicle screw insertion were safe and accurate., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Robot-assisted pedicle screw insertion has been slowly gaining popularity in the spine surgery community. In previous studies, robotics has been shown to increase accuracy and reduce complication rates compared to other navigation technologies, although those studies have been conducted using traditional trajectories for pedicle screw insertion. We present a surgical video in which a robotics system (Mazor X; Mazor Robotics Ltd, Caesarea, Israel) was used to create cortical bone trajectories for the insertion of the screws. The patient in this case is a 52-yr-old woman with severe L4-5 disc herniation requiring a transforaminal interbody fusion with the insertion of pedicle screws. The robotic system's scan-and-plan technique was utilized, in which an intraoperative computed tomography (CT) scan generates a real-time operative plan. Other techniques for inserting pedicle screws using cortical bone trajectories include CT navigation and fluoroscopic guidance. These techniques allow the surgeon to manually direct the screw under precise guidance in multiple planes, although the surgeon is still using all 6 degrees of freedom the human hand provides. With robotic guidance, a pilot hole is drilled, which eliminates 4 of 6 degrees of freedom, which can potentially reduce the risk of misplaced screws. To our knowledge, this is the first video demonstrating pedicle screw insertion through cortical bone trajectories using robotic guidance. Future studies are warranted to compare cortical bone trajectory insertion using different navigation techniques to determine the long-term efficacy of each technique. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: To study the differences between robot-guided (Mazor X, Mazor Robotics Ltd., Caesarea, Israel) and 3-dimensional (3D) computed tomography (CT) navigation (O-arm Surgical Imaging System, Medtronic, Minneapolis, Minnesota, USA) for the insertion of pedicle screws., Methods: We reviewed the charts of 50 patients who underwent robot-guided pedicle screw insertion (between May 2017-October 2017), and 49 patients who underwent 3D-CT navigation pedicle screw insertion (between September 2015-August 2016). Variables included were age, sex, body mass index, blood loss, length of stay, lumbar level(s), operation time, fluoroscopy time, radiation dose, accuracy, and time-per-screw placement., Results: Mean ages were 59.3 years in the robotic group and 58.2 years in the 3D-CT navigation group. Mean was 30.7 kg/m 2 in the robotic group and 32.1 kg/m 2 in the 3D-CT navigation group. Mean time-per-screw placement was 3.7 minutes for the robotic group and 6.8 minutes for the 3D-CT navigation group, P < 0.001. In the robotic group, 189 of 190 screws were placed with Ravi grade I accuracy, and 1 was grade II. In the 3D-CT navigation group, 157 of 165 screws were Ravi grade I, and 8 were grade II (P = 0.11). Fluoroscopy time (P < 0.001), time-per-screw placement (P < 0.001), and length of stay (P < 0.001) were significantly lower in the robotic group., Conclusions: Both technologies are safe and accurate. Robotic technology exposed patients to less fluoroscopy time, decreased time-per-screw placement and shorter hospital stay than 3D-CT navigation. Further studies are warranted to verify our results., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study was performed to assess the incidence and intraoral distribution of different mucosal lesions in a representative population. Retrospective review of clinical notes and assessment of histology reports of patients were performed, who presented with different oral lesions to University Hospital Galway, between January 2007 and December 2008.Of the 106 histology reports evaluated, 94 were identified as benign lesions while 12 were malignant lesions. 96 of these patients were referred from G.P services, 6 patients were referred from other departments while 4 patients came through emergency department by self referral. The numbers and incidence of the commonest lesions in order of frequency were chronic inflammation 20 (18.8%), papilloma 19 (17.1%), fibroma 09 (8.4%), mucocele 09 (8.4%) and leukoplakia 08 (7.5%).We concluded that majority of the presented oral lesions are benign (88.%). Chronic inflammation (18.8%) is the commonest benign oral lesion and all white lesions which represents 34% of oral lesions are not true leukoplakia.

Background: Takayasu arteritis (TA) is an idiopathic large-vessel vasculitis that can result in significant morbidity and mortality secondary to progressive stenosis and occlusion. Monitoring disease progression is crucial to preventing relapse, but is often complicated by the lack of clinical symptoms in the setting of active disease. Although acute phase reactants such as ESR and CRP are generally used as an indicator of inflammation and disease activity, mounting evidence suggests that these markers cannot reliably distinguish active from inactive TA., Case Presentation: We report a 24-year-old Hispanic female with a 5-year history of TA who presented with stroke-like symptoms and evidence of left MCA occlusion on imaging, despite a history of decreasing inflammatory markers. CTA revealed complete occlusion of the left common carotid artery, left subclavian, and left MCA from their origins. It also revealed a striking compensatory circulation supplying the left anterior circulation as well as the left subclavian as a response to progressive stenosis., Conclusion: Monitoring ESR and CRP levels alone may not be a reliable method to evaluate disease progression in patients with TA, and should be taken in context with both patient's clinical picture and the imaging. We recommend that serial imaging be performed regularly in the setting of active disease to monitor progression and allow for immediate therapy in response to evidence of disease advancement, with a relaxation of the imaging interval once the disease is presumed inactive.

Activation of angiotensin-converting enzyme 2 (ACE2), production of angiotensin-(1-7) [Ang-(1-7)] and stimulation of the Ang-(1-7) receptor Mas exert beneficial actions in various peripheral cardiovascular diseases, largely through opposition of the deleterious effects of angiotensin II via its type 1 receptor. Here we considered the possibility that Ang-(1-7) may exert beneficial effects against CNS damage and neurological deficits produced by cerebral ischaemic stroke. We determined the effects of central administration of Ang-(1-7) or pharmacological activation of ACE2 on the cerebral damage and behavioural deficits elicited by endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO), a model of cerebral ischaemia. The results of the present study demonstrated that intracerebroventricular infusion of either Ang-(1-7) or an ACE2 activator, diminazine aceturate (DIZE), prior to and following ET-1-induced MCAO significantly attenuated the cerebral infarct size and neurological deficits measured 72 h after the insult. These beneficial actions of Ang-(1-7) and DIZE were reversed by co-intracerebroventricular administration of the Mas receptor inhibitor, A-779. Neither the Ang-(1-7) nor the DIZE treatments altered the reduction in cerebral blood flow elicited by ET-1. Lastly, intracerebroventricular administration of Ang-(1-7) significantly reduced the increase in inducible nitric oxide synthase mRNA expression within the cerebral infarct that occurs following ET-1-induced MCAO. This is the first demonstration of cerebroprotective properties of the ACE2-Ang-(1-7)-Mas axis during ischaemic stroke, and suggests that the mechanism of the Ang-(1-7) protective action includes blunting of inducible nitric oxide synthase expression.

Splenic rupture is a rare but potentially fatal complication of infectious mononucleosis. Athletes returning to contact sports following infectious mononucleosis are at potential risk of splenic rupture secondary to abdominal trauma. No clear consensus exists as to when it is safe to allow these athletes to return to contact sports. Suggested periods of abstinence have ranged from 2 weeks to 6 months. We outline our experiences with the use of abdominal ultrasonography at 1 month after the diagnosis of infectious mononucleosis as a means of determining when athletes can safely return to contact sports. Our study group was made up of 19 such patients (mean age: 16.7 yr). We found that 16 of these patients (84%) had normal splenic dimensions on ultrasonography 1 month after diagnosis, and they were therefore allowed to return to contact sports. While the remaining 3 patients had an enlarged spleen at 1 month, their splenic dimensions had all returned to normal when ultrasonographic examination was repeated at 2 months postdiagnosis. We conclude that serial abdominal ultrasonography allows for informed decision making in determining when athletes can safely return to contact sports following infectious mononucleosis.

Objective: To outline the authors' experiences with performing laryngotracheoplasty as an alternative to tracheostomy in neonates and infants with symptomatic subglottic stenosis (SGS)., Study Design: Case series with chart review., Setting: A tertiary referral pediatric hospital., Subjects and Methods: Patients younger than 12 months undergoing single-stage laryngotracheoplasty for SGS at the authors' institution over a 3-year period., Results: Ten patients (8 boys and 2 girls) underwent single-stage laryngotracheoplasty during the study period. There were 9 cases of acquired SGS and 1 case of congenital SGS. Eight patients had grade III SGS, and 2 patients had grade II SGS. In 9 of 10 patients, the procedure performed was an anterior cricoid split (ACS) and posterior cricoid split (PCS), with the placement of an anterior thyroid ala cartilage graft. One patient underwent ACS and PCS with the placement of a posterior rib cartilage graft, in combination with a right vocal cord lateralization. The mean period of intubation after surgery was 6.8 days (range, 5-9 days). Nine of 10 patients had a complete resolution of their airway symptoms following airway surgery, with a mean duration of follow-up of 305 days (range, 30-780 days). One patient required the placement of a tracheostomy tube 69 days postoperatively due to a failure to wean from ventilation in the setting of multiple comorbidities., Conclusion: Laryngotracheoplasty is a safe and effective alternative to long-term tracheostomy in infants and neonates with symptomatic SGS.

Studies show 60% of patients with newly diagnosed Head & Neck Squamous Cell Cancer in Ireland, present with advanced disease. A poor level of knowledge and awareness among the public of Head & Neck Cancer, is an important consideration in the often delayed presentation for medical attention in many of these cases. Our study surveyed 200 members of the public to assess their knowledge and awareness of Head & Neck Cancer. One hundred and forty (70%) of respondents had never encountered the term "Head & Neck Cancer". One hundred and forty six (73%) failed to identify excessive alcohol consumption as a risk factor. Less than 100 (50%) would have concern about persisting hoarseness or a prolonged oral ulcer. An urgent need exists to raise awareness of Head & Neck Cancer among the public in Ireland.

Objective: We report the rare case of an oesophageal foreign body which lodged above the site of oesophageal compression by a double aortic arch., Methods: Case report and a review of the literature surrounding the classification, embryology, diagnosis and management of vascular rings and slings., Results: An eight-month-old male infant presented with symptoms of tracheal compression following ingestion of an oesophageal foreign body. Following removal of the oesophageal foreign body, the infant's symptoms improved initially. However, subsequent recurrence of respiratory symptoms lead to a repeat bronchoscopy and the diagnosis of a coexisting double aortic arch, causing tracheal and oesophageal compression., Conclusion: To our knowledge, this is only the second reported case of a double aortic arch being diagnosed in a patient following removal of an oesophageal foreign body.

Acute otitis media (AOM) is diagnosed on the basis of acute onset of pain and fever; a red, bulging tympanic membrane; and middle ear effusion. AOM is managed with analgesia (paracetamol or non-steroidal anti-inflammatory drugs). Antibiotic therapy is minimally effective for most patients; it is most effective for children < 2 years with bilateral otitis media and for children with discharging ears. National guidelines recommend antibiotic therapy for Indigenous children with AOM. Evidence for corticosteroids, topical analgesia and xylitol are scant. Otitis media with effusion (OME) is diagnosed as the presence of middle ear effusion (type B tympanogram or immobile tympanic membrane on pneumatic otoscopy) without AOM criteria. Well children with OME with no speech and language delays can be observed for the first 3 months; perform audiological evaluation and refer to an ear, nose and throat (ENT) specialist if they have bilateral hearing impairment > 30 dB or persistent effusion. Children with effusions persisting longer than 3 months can benefit from a 2-4-week course of amoxycillin. Chronic suppurative otitis media is a chronic discharge through a tympanic membrane perforation. It is managed with regular ear cleaning (dry mopping or povidone-iodine [Betadine] washouts) until discharge resolves; topical ear drops (eg, ciprofloxacin); audiological evaluation; and ENT review.

Objective: Supraglottoplasty is well documented as an effective procedure in the management of moderate to severe laryngomalacia. Traditionally assessed outcomes in the treatment of laryngomalacia include: reduced stridor, improved feeding and a resumption of weight-gain. Previous authors have documented the use of polysomnography in assessing the severity of paediatric laryngeal abnormalities. The aim of the current study was to objectively assess the efficacy of supraglottoplasty for laryngomalacia by comparing data from pre- and post-operative polysomnography., Methods: A retrospective review was performed of patients undergoing supraglottoplasty for laryngomalacia at a tertiary referral paediatric hospital over a 35-month period. Patients were required to have undergone full overnight polysomnography both before and after supraglottoplasty. Pre- and post-operative polysomnographic results were compared and the statistical significance between mean values was determined., Results: From a total of 46 patients, 10 were suitable for inclusion into the study. Mean age at first presentation was 2 months and 19 days (range 30-134 days). The surgical procedure performed was bilateral division of aryepiglottic folds alone in 1 patient (1/10), bilateral division of aryepiglottic folds and bilateral trimming of arytenoid mucosa in 5 patients (5/10) and bilateral aryepiglottic fold division, bilateral arytenoid mucosal trimming and epiglottic trimming or epiglottopexy in 4 patients (4/10). Statistically significant improvements occurred in mean values for Total Sleep Time (TST) (P=0.049), Lowest Oxygen Saturation Levels (SpO2 nadir) (P=0.006), Obstructive Apnoea Hypopnoea Index (OAHI) (P=0.009) and Respiratory Disturbance Index (RDI) (P=0.002), following supraglottoplasty. An improvement in mean Transcutaneous Carbon Dioxide (TcCO2) value occurred, but did not achieve statistical significance (57.1 vs. 52.8) (P=0.259). The mean age at which post-operative polysomnography confirmed a reversal of abnormal respiratory parameters following surgery was 5 months and 18 days., Conclusions: Polysomnography is an effective method for objectively assessing the efficacy of supraglottoplasty for laryngomalacia. Supraglottoplasty effectively reverses the abnormal respiratory parameters occurring in moderate to severe laryngomalacia.

Endogenous levels of angiotensin II (Ang II) are increased in the cortex and hypothalamus following stroke, and Ang II type 1 receptor blockers (ARBs) have been shown to attenuate the deleterious effects in animal stroke models using middle cerebral artery (MCA) intraluminal occlusion procedures. However, the endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO) model of cerebral ischaemia is thought to more closely mimic the temporal events of an embolic stroke. This method provides rapid occlusion of the MCA and a gradual reperfusion that lasts for 16-22 h. The aim of the present study was to evaluate whether systemic administration of an ARB prior to ET-1-induced MCAO would provide cerebroprotection during this model of ischaemic stroke. Injection of 3 microl of 80 microM ET-1 adjacent to the MCA resulted in complete occlusion of the vessel that resolved over a period of 30-40 min. Following ET-1-inducedMCAO, rats had significant neurological impairment, as well as an infarct that consisted of 30% of the ipsilateral grey matter. Systemic pretreatment with 0.2 mg kg(-1) day(-1) candesartan for 7 days attenuated both the infarct size and the neurological deficits caused by ET-1-induced MCAO without altering blood pressure. This study confirms the cerebroprotective properties of ARBs during ischaemic stroke and validates the ET-1-induced MCAO model for examination of the role of the brain renin-angiotensin system in ischaemic stroke.

The purpose of this study was to investigate the effects of a light, high-repetition resistance-training program on skinfold thicknesses and muscular strength in women. Thirty-nine active women (mean age 38.64 +/- 4.97 years) were randomly placed into a resistance-training group (RT; n = 20) or a control group (CG; n = 19). The RT group performed a resistance-training program called Bodymax for 1 hour, 3 d.wk(-1), which incorporated the use of variable free weights and high repetitions in a group setting. The CG group continued its customary aerobic training for 1 hour 3 d.wk(-1). Five skinfold and 7 muscular strength measures were determined pretraining and after 12 weeks of training. Sum of skinfolds decreased (-17 mm; p < 0.004) and muscular strength increased (+57.4 kg; p < 0.004) in the RT group. Effect sizes for individual skinfold sites and strength measures were "medium" and "high," respectively. Bodymax is an effective resistance-training program for reducing skinfold thickness and increasing muscular strength in active women. Therefore, women with a similar or lower-activity status should consider incorporating such training into their regular fitness programs.

We examined the effect of levamisole (LMS) on the proliferative response and interleukin-2 (IL-2) concentration in OKT3-, phytohemagglutinin-, and concanavalin-A-stimulated lymphocyte cultures. Although proliferative response was enhanced in lymphocyte cultures stimulated in the presence of LMS, similar levels of IL-2 were observed in stimulated and unstimulated cultures. The mechanism of the enhancement effect of LMS on proliferative response was further characterized by studying its effects on the growth of IL-2-dependent CTLL-2 cells in culture. Since this cell line has been shown to require 2-mercaptoethanol (2-ME) for normal growth in recombinant IL-2, the effect of LMS on several parameters of its growth was compared with that of 2-ME. Unlike 2-ME, LMS did not enhance 35S-cystine uptake. Both compounds increased thiol concentration in the cell culture, but (oxidized) 2-ME induced a greater increase. Generally, the effects of LMS on CTLL-2 growth were quite similar to those of structurally unrelated compounds known to have antioxidant properties, and the demonstrated thiol requirement of this cell line for growth in recombinant IL-2 was met by substituting LMS for 2-ME. When the effect of LMS on IL-2 receptor (IL-2R) expression in CTLL-2 cells was examined by a receptor-ligand binding assay involving low levels (10-80 pM) of 125IL-2, a modest increase in the level of IL-2R expression was observed. The biologically active high-affinity IL-2R complex is believed to be preferentially bound at the low levels of 125IL-2 used here, suggesting a functional relevance for this effect of LMS. These observations should be useful in minimizing the cost and duration of in vitro expansion of lymphocytes for use in adoptive immunotherapy and should be applicable in improving the response of immunologically impaired patients to immunotherapy.

We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirteen rifamycin SV derivatives containing 3'-alkylaminomethyl substituents fail to inhibit the activities of the simian sarcoma virus Type 1 DNA polymerase, and of cellular DNA, RNA, and poly(A) polymerases prepared from NIH Swiss mouse embryos. These compounds show a range in their toxicities for NIH Swiss mouse 3T3 cells and in their capacities to inhibit production of foci of morphologically altered cells by murine sarcoma virus (MSV). Three compounds--the N-methyl-N-hydroxyethylaminomethyl, the N,N-dimethyl-aminomethyl, and the N4-methylpiperazinomethyl rifamycin derivatives--are comparable to adenine arabinoside and ribavirin in their toxicity for 3T3 cells, but these compounds show superior focus inhibition. These compounds inhibit oncornavirus production apparently by exacerbation of a delay in growth that results from infection of 3T3 cells with MSV.

A hypothesis is presented that cellular proto-oncogenes encode proteins that play a regulatory role in embryonic development and in the terminal differentiations of cells in various tissues and that alterations in these genes yield oncogenes whose expression results in neoplasia. The hypothesis suggests that study of the disturbance in cell regulation introduced by oncogenes could permit the rational design of inhibitors capable of restoring neoplastic cells to normal differentiation lineages. Proteins encoded by oncogenes may be immunogenic and thus provide diagnostic markers in the tumor-bearing host.

The antigenicity and composition of chromatins differ markedly in chromatin preparations obtained by different procedures. Rat Novikoff hepatoma chromatin (NC) obtained by the "salt precipitation" and the micrococcal nuclease digestion procedures using significant levels of EDTA and NaCl each shows a common complement fixation (CF) capacity, exceeding chromatin preparations obtained from normal rat liver when tested with rabbit antisera raised to dehistonized NC. In contrast, "structured" NC preparations, which have been postulated to retain a native physical conformation, show minimal CF capacity when tested with the same antiserum but show high CF following elution of histones. While further progressive elution of non-histone proteins (NHPs) did not alter the CF capacity per unit DNA, the completely separated DNA and NHP fractions each showed minimal CF. The data suggest that the antigens detected in the CF assay predominantly represent an artifactual but specific complex of DNA and NHP arising from a denaturation of the native chromatin following elution of metal ions or histones. A qualitatively similar profile of NHPs in salt-precipitated NCs shows a range of total protein/DNA ratios, suggesting that the NHPs found in chromatin preparations may not be intrinsic to the native chromatin structure.

Monoclonal antibody technology permits the preparation of tumor-specific immunoglobulin reagents that can be used directly in tumor therapy or that can be coupled to various chemotherapeutic drugs or toxins to aid in their delivery to the tumor site and thus enhance their therapeutic effectiveness. Additionally, recombinant DNA technology has facilitated the economic production of rare lymphokines (e.g., interleukin 2, interferon alpha and interferon gamma) or cytokines (tumor necrosis factor, lymphotoxin) that can either modulate the host immune response or kill tumor cells, respectively. These developments collectively have led to the development of a fourth modality for treatment of human cancers--biotherapy--as an addition to surgery, radiation, and chemotherapy modalities. This paper presents the rationale and emerging practice of the biotherapy of cancer and documents early clinical results, including the treatment of metastatic renal carcinoma at the Biological Therapy Institute.