Acoustic resonance therapy is safe and effective for the treatment of nasal congestion in rhinitis: A randomized sham-controlled trial.

BACKGROUND: Acoustic resonance therapy (ART) is a novel vibrational treatment that delivers patient-specific resonant frequency acoustic energy to the sinonasal cavities. In a pilot study, ART was effective for the acute treatment of nasal congestion. We conducted a sham-controlled randomized trial to validate the efficacy of ART when administered daily for 2 weeks. METHODS: A total of 52 adult patients were enrolled in a multi-center, randomized, double-blinded, sham-controlled, interventional study evaluating ART administered by a vibrational headband. Patients received either active treatment or a non-therapeutic sham treatment twice daily over 2 weeks. Clinical endpoints were the average change in nasal congestion sub-score of the Total Nasal Symptom Score (TNSS) and the average change in composite TNSS. RESULTS: ART resulted in a significantly greater mean change in the nasal congestion sub-score compared to sham (-0.87 [95% confidence interval [CI] -1.11, -0.62] vs. -0.44 [95% CI -0.64, -0.23], p = 0.008). ART also resulted in a significantly greater reduction in the composite TNSS versus sham, (-2.85 [95% CI -3.85, -1.85], vs. -1.32 [95% CI -2.27, -0.36], p = 0.027). The response rate, determined by a nasal congestion sub-score minimal clinically important difference of 0.23, was 80.8% for ART and 46.2% for sham, with an adjusted risk ratio of 1.95 (95% CI 1.26, 3.02, p = 0.003) in favor of ART. Safety endpoints showed no adverse events. CONCLUSION: ART is a safe and effective non-pharmacologic alternative for the treatment of nasal congestion.

An exploratory study to understand faculty members' perceptions and challenges in online teaching.

The government of the United Arab Emirates (UAE) considers technology to be one of the main pillars of its vision for moving towards a knowledge-based society. Due to several factors such as globalisation, demand for information technology infrastructure and COVID-19 lockdowns, e-learning has become a popular method of delivery across higher education institutions in the UAE. In a first step, the authors of this article conducted a systematic review of existing literature (49 items published between 1999 and 2020). They found that the existing literature on online learning predominantly focuses on student-specific challenges, while there is still a dearth of published work covering faculty members' specific challenges in facilitating online learning in the UAE. The second part of this exploratory study drew on stakeholders' reflections of several years of designing and delivering online courses, analysing faculty members' perspectives on online teaching and learning in the UAE. The authors present their qualitative research, which involved open-ended semi-structured interviews with 15 faculty members, followed by a thematic analysis of their responses using NVivo 12 pro software. The most critical themes which emerged were learners' expectations, culture, perception, pedagogy and technology. The article also reveals how these topics contribute to the various strategies for seamless adoption and delivery of online education in the UAE.

Une étude exploratoire pour comprendre les perceptions et les défis des enseignants dans l'enseignement en ligne ­ Le gouvernement des Émirats Arabes Unis (EAU) considère la technologie comme l'un des principaux piliers de son projet d'évolution vers une société axée sur la connaissance. En raison de plusieurs facteurs tels que la mondialisation, la demande d'infrastructures pour les technologies de l'information et les confinements dus au COVID-19, l'apprentissage en ligne est devenu une méthode d'enseignement populaire dans les établissements d'enseignement supérieur aux EAU. Dans un premier temps, les auteurs de cet article ont procédé à une revue systématique de la littérature existante (49 articles publiés entre 1999 et 2020). Ils ont constaté que la littérature existante sur l'apprentissage en ligne se concentre principalement sur les défis propres aux étudiants, alors qu'il y a encore peu de travaux couvrant les défis spécifiques aux membres du corps enseignant pour faciliter l'apprentissage en ligne aux EAU. La deuxième partie de cette étude exploratoire s'est appuyée sur les réflexions de différents acteurs sur plusieurs années de conception et d'enseignement de cours en ligne, analysant les perspectives des membres du corps enseignant sur l'enseignement et l'apprentissage en ligne aux EAU. Les auteurs présentent leur recherche qualitative, qui comprend des entretiens semi-structurés ouverts avec 15 membres du corps enseignant, suivis d'une analyse thématique de leurs réponses à l'aide du logiciel NVivo 12 pro. Les thèmes les plus importants qui ont émergé ont été les attentes des apprenants, la culture, la perception, la pédagogie et la technologie. L'article révèle également comment ces sujets contribuent aux diverses stratégies pour une adoption et une diffusion harmonieuses de l'enseignement en ligne aux EAU.

Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer.

BACKGROUND: Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. PATIENTS AND METHODS: This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m2), or, weekly paclitaxel (80 mg/m2) over 18 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). RESULTS: 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70-1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69-1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68-1.75, P = 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel. CONCLUSIONS: Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Temporal Trends in Deep Surgical Site Infections After Six Orthopaedic Procedures Over a 12-year Period Within a US-based Healthcare System.

INTRODUCTION: Centers of excellence and bundled payment models have driven perioperative optimization and surgical site infection (SSI) prevention with decolonization protocols and antibiotic prophylaxis strategies. We sought to evaluate time trends in the incidence of deep SSI and its causative organisms after six orthopaedic procedures in a US-based integrated healthcare system. METHODS: We conducted a population-level time-trend study using data from Kaiser Permanente's orthopaedic registries. All patients who underwent primary anterior cruciate ligament reconstruction (ACLR), total knee arthroplasty (TKA), elective total hip arthroplasty (THA), hip fracture repair, shoulder arthroplasty, and spine surgery were identified (2009 to 2020). The annual incidence of 90-day deep SSI was identified according to the National Healthcare Safety Network/Centers for Disease Control and Prevention guidelines with manual chart validation for identified infections. Poisson regression was used to evaluate annual trends in SSI incidence with surgical year as the exposure of interest. Annual trends in overall incidence and organism-specific incidence were considered. RESULTS: The final study sample was composed of 465,797 primary orthopaedic procedures. Over the 12-year study period, a decreasing trend in deep SSI was observed for ACLR and hip fracture repair. Although there was variation in incidence rates for specific operative years for TKA, elective THA, shoulder arthroplasty, and spine surgery, no consistent decreasing trends over time were found. Decreasing rates of Staphylococcus aureus infections over time after hip fracture repair, shoulder arthroplasty, and spine surgery and decreasing trends in antibiotic resistance after elective THA and spine surgery were also observed. Increasing trends of polymicrobial infections were observed after TKA and Cutibacterium acnes after elective THA. CONCLUSIONS: The overall incidence of deep SSI after six orthopaedic procedures was rare. Decreasing SSI rates were observed for ACLR and hip fracture repair within our US-based healthcare system. Polymicrobial infections after TKA and Cutibacterium acnes after elective THA warrant closer surveillance. LEVEL OF EVIDENCE: IV.

RNR inhibitor binding studies of Chlamydia felis: insights from in silico molecular modeling, docking, and simulation studies.

Chlamydia felis is the primary cause of chronic conjunctivitis without respiratory infections in cats, making conjunctiva as its primary target. It is a Gram-negative obligate intracellular bacterium that cannot survive outside the host cell. C. felis can be found worldwide and its zoonotic potential is a known phenomenon. The scope of zoonoses, its scale, and their impact experiencing today has no historical precedence. Among the identified 1415 human pathogens 868 have a zoonotic origin making it to 61%. Although with appropriate drug administration there are instances of re-occurrence of chlamydial infections, the emergence of heterotypic antimicrobial resistance to antibiotics targeting rRNA due to mutations has further complicated the diagnosis and treatment of chlamydial infections. Ribonucleotide-diphosphate reductase subunit beta (RNR) is one of the crucial target proteins of the bacterial pathogens essential in the synthesis of deoxyribonucleotides. Our current study primarily focuses on modeling the target structure through homology modeling. Further, the validated model is complexed with the specific inhibitor Cladribine through sequence-based ligand search. Docking of the identified ligand was performed to identify the different modes of interactions with amino acids present in the prioritized binding pockets. Validation of the binding modes is carried out through molecular dynamics (MD) simulations for the best binding pose with a high binding score. MD simulation study demonstrated the stability of the docked complex considered in this study. The findings from this study may be helpful in drug repurposing and novel drug research in the scenario of resistance to currently practiced antibiotics.Communicated by Ramaswamy H. Sarma.

Fatal acute hepatic failure secondary to thrombotic portal venopathy after commencing abemaciclib and fulvestrant treatment for advanced breast carcinoma: a unique autopsy finding.

We present an autopsy case of hepatic thrombotic portal venopathy resulting in decompensated liver failure and death which occurred rapidly after commencing abemaciclib and fulvestrant chemotherapy for advanced invasive lobular carcinoma of the breast. The diagnosis was confirmed histologically. This is the first reported case of such a finding. We suggest that further cases displaying this previously unpublished pattern are collated in order that we may begin to investigate the underlying etiological mediators.

Increasing cardiopulmonary aerobic activity improves motor cognitive response time: An inference from preliminary one-group pretest-posttest quasi-experimental study.

Motor cognitive response time (MCRT) is the time elapsed between presenting a stimulus and the time taken by that individual to respond to that stimulus through a motor performance. After completing aerobic exercise, there are various changes that takes place, one of which might be change in cognitive function. Whether cardiopulmonary aerobic activity/capacity has an impact on MCRT is not explored yet.

Biomechanical Effects of Human Lumbar Discography: In Vitro Experiments and Their Finite Element Validation.

STUDY DESIGN: An experimental and computational finite element analysis of human lumbar spine discography and its resulting effects on disk biomechanics. OBJECTIVE: To characterize the changes in stress and displacement of the human lumbar spine disks after puncture due to discography. SUMMARY OF BACKGROUND DATA: Discography of the intervertebral disk (IVD) may be used to diagnose pathology of the disk and determine whether it may be a source for chronic back pain. It has recently been suggested that discography may lead to IVD degeneration, and has been a cause of controversy among spine care physicians. MATERIALS AND METHODS: Both in vivo experiment using cadaveric specimens and a finite element model of the same L3-L5 lumbar spine was developed using computed tomography scans. Discography was simulated in the model as an area in the disk affected by needle puncture. The material properties in the nucleus pulposus were adjusted to match experimental data both before and after puncture. RESULTS: Puncture of the IVD leads to increased deformation and increased stresses in the annulus fibrosis region of the disk. Pressure in the nucleus pulposus was found to decrease after puncture. Experimental and computational results correlated well. CONCLUSIONS: Puncturing the IVD changes disk biomechanics and hence may lead to progressive spine degenerations in particular in the punctured disks.

An unusual flare of anti-synthetase syndrome during concurrent trastuzumab therapy given for recurrent breast cancer.

We present the case of a patient with relapsing anti-synthetase syndrome (ASS) that may have been triggered by monoclonal antibody trastuzumab therapy given for breast cancer. A 52-year-old female with a history of anti-Jo1-associated ASS went into remission with glucocorticoids and mycophenolate mofetil. Her past history included invasive ductal carcinoma of the right breast that was fully treated six years prior to the onset of ASS. She subsequently developed recurrent right-sided breast cancer that was treated with right mastectomy and six cycles of cyclophosphamide-docetaxel chemotherapy. She commenced adjuvant trastuzumab and letrozole therapy, and following the sixth injection of trastuzumab, she was admitted with clinical features consistent with a flare of ASS, which included swinging fever, interstitial lung disease, myositis, and possible subclinical myocarditis, despite recent treatment with cyclophosphamide. She responded to intravenous IV methylprednisolone followed by increased doses of oral glucocorticoids, and she remains stable on immunomodulatory treatment and letrozole monotherapy given for breast cancer. This report provides a concise overview of ASS along with other cases of cardiac and pulmonary diseases attributed to trastuzumab therapy reported in the medical literature.

Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer.

FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian cancers and have clinicopathological significance in patients. We comprehensively investigated FEN1 mRNA expression in multiple cohorts of breast cancer [training set (128), test set (249), external validation (1952)]. FEN1 protein expression was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER positive breast cancers and 156 ovarian epithelial cancers. FEN1 mRNA overexpression was highly significantly associated with high grade (p = 4.89 × 10(-57)), high mitotic index (p = 5.25 × 10(-28)), pleomorphism (p = 6.31 × 10(-19)), ER negative (p = 9.02 × 10(-35)), PR negative (p = 9.24 × 10(-24)), triple negative phenotype (p = 6.67 × 10(-21)), PAM50.Her2 (p = 5.19 × 10(-13)), PAM50. Basal (p = 2.7 × 10(-41)), PAM50.LumB (p = 1.56 × 10(-26)), integrative molecular cluster 1 (intClust.1) (p = 7.47 × 10(-12)), intClust.5 (p = 4.05 × 10(-12)) and intClust. 10 (p = 7.59 × 10(-38)) breast cancers. FEN1 mRNA overexpression is associated with poor breast cancer specific survival in univariate (p = 4.4 × 10(-16)) and multivariate analysis (p = 9.19 × 10(-7)). At the protein level, in ER positive tumours, FEN1 overexpression remains significantly linked to high grade, high mitotic index and pleomorphism (ps < 0.01). In ER negative tumours, high FEN1 is significantly associated with pleomorphism, tumour type, lymphovascular invasion, triple negative phenotype, EGFR and HER2 expression (ps < 0.05). In ER positive as well as in ER negative tumours, FEN1 protein overexpression is associated with poor survival in univariate and multivariate analysis (ps < 0.01). In ovarian epithelial cancers, similarly, FEN1 overexpression is associated with high grade, high stage and poor survival (ps < 0.05). We conclude that FEN1 is a promising biomarker in breast and ovarian epithelial cancer.

Monoblock all-polyethylene tibial components have a lower risk of early revision than metal-backed modular components.

BACKGROUND AND PURPOSE: With younger patients seeking reconstructions and the activity-based demands placed on the arthroplasty construct, consideration of the role that implant characteristics play in arthroplasty longevity is warranted. We therefore evaluated the risk of early revision for a monoblock all-polyethylene tibial component compared to a metal-backed modular tibial construct with the same articular geometry in a sample of total knee arthroplasties (TKAs). We evaluated risk of revision in younger patients (< 65 years old) and in older patients (≥ 65 years old). METHOD: Fixed primary TKAs with implants from a single manufacturer, performed between April 2001 and December 2010, were analyzed retrospectively. Patient characteristics, surgeon, hospital, procedure, and implant characteristics were compared according to tibial component type (monoblock all-polyethylene vs. metal-backed modular). All-cause revisions and aseptic revisions were evaluated. We used descriptive statistics and Cox regression models. RESULTS: 27,657 TKAs were identified, 2,306 (8%) with monoblock and 25,351 (92%) with modular components. In adjusted models, the risk of early all-cause revision (hazard ratio (HR) = 0.5, 95% confidence interval (CI): 0.3-0.8) and aseptic revision (HR = 0.6, CI: 0.3-1.2) was lower for the monoblock cohort than for the modular cohort. In older patients, the early risk of all-cause revision was 0.6 (CI: 0.4-1.0) for the monoblock cohort compared to the modular cohort. In younger patients, the adjusted risk of all-cause revision (HR = 0.3, CI: 0.1-0.7) and of aseptic revision (HR = 0.3, CI: 0.1-0.7) were lower for the monoblock cohort than for the modular cohort. INTERPRETATION: Overall, monoblock tibial constructs had a 49% lower early risk of all-cause revision and a 41% lower risk of aseptic revision than modular constructs. In younger patients with monoblock components, the early risk of revision for any cause was even lower.

Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells.

INTRODUCTION: Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is a key sensor of single-stranded DNA associated with stalled replication forks and repair intermediates generated during DNA repair. XRCC1 is a critical enzyme in single strand break repair and base excision repair. XRCC1-LIG3 complex is also an important contributor to the ligation step of the nucleotide excision repair response. METHODS: In the current study, we investigated synthetic lethality in XRCC1 deficient and XRCC1 proficient Chinese Hamster ovary (CHO) and human ovarian cancer cells using ATR inhibitors (NU6027). In addition, we also investigated the ability of ATR inhibitors to potentiate cisplatin cytotoxicity in XRCC1 deficient and XRCC1 proficient CHO and human cancer cells. Clonogenic assays, alkaline COMET assays, γH2AX immunocytochemistry, FACS for cell cycle as well as FITC-annexin V flow cytometric analysis were performed. RESULTS: ATR inhibition is synthetically lethal in XRCC1 deficient cells as evidenced by increased cytotoxicity, accumulation of double strand DNA breaks, G2/M cell cycle arrest and increased apoptosis. Compared to cisplatin alone, combination of cisplatin and ATR inhibitor results in enhanced cytotoxicity in XRCC1 deficient cells compared to XRCC1 proficient cells. CONCLUSIONS: Our data provides evidence that ATR inhibition is suitable for synthetic lethality application and cisplatin chemopotentiation in XRCC1 deficient ovarian cancer cells.

Are DNA repair factors promising biomarkers for personalized therapy in gastric cancer?

Chronic inflammation is a driving force for gastric carcinogenesis. Reactive oxygen species (ROS) generated during the inflammatory process generates DNA damage that is processed through the DNA repair pathways. In this study, we profiled key DNA repair proteins (single-strand-selective monofunctional uracil-DNA glycosylase 1 [SMUG1], Flap endonuclease 1 [FEN1], X-ray repair cross-complementing gene 1 [XRCC1], and Ataxia telangiectasia mutated [ATM]) involved in ROS-induced oxidative DNA damage repair in gastric cancer and correlated to clinicopathological outcomes. High expression of SMUG1, FEN1, and XRCC1 correlated to high T-stage (T3/T4) (p-values: 0.001, 0.005, and 0.02, respectively). High expression of XRCC1 and FEN1 also correlated to lymph node-positive disease (p-values: 0.009 and 0.02, respectively). High expression of XRCC1, FEN1, and SMUG1 correlated with poor disease-specific survival (DSS) (p-values: 0.001, 0.006, and 0.05, respectively) and poor disease-free survival (DFS) (p-values: 0.001, 0.001, and 0.02, respectively). Low expression of ATM correlated to lymph node positivity (p=0.03), vascular invasion (p=0.05), and perineural invasion (p=0.005) and poor DFS (p=0.001) and poor DSS (p=0.003). In the multivariate Cox model, high XRCC1 and low ATM were independently associated with poor survival (p=0.008 and 0.011, respectively). Our observation supports the hypothesis that DNA repair factors are promising biomarkers for personalized therapy in gastric cancer.

Case report: incisional hernia as a complication of extreme lateral interbody fusion.

BACKGROUND CONTEXT: Minimal access surgery is becoming more popular for spinal fusion because of a lower theoretical risk of complications and shorter postoperative recovery period, compared with the traditional open approach. The lateral approach uses retroperitoneal transpsoas access to the vertebra, obviating the need for an approach surgeon and minimizing muscular disruption, thus allowing a quicker recovery. Initial reports of the lateral transpsoas procedure described few complications. However, a number of complications have subsequently been documented. To our knowledge, there has not been a description of an incisional hernia after this approach. PURPOSE: To report the rare complication of an incisional hernia after a minimal access lateral transpsoas approach for lumbar interbody fusion. STUDY DESIGN: Case report. METHODS: We reviewed the hospital charts, radiographs, and intraoperative photographs of a patient who underwent a minimally invasive lateral approach lumbar spine fusion with a subsequent incisional hernia that necessitated laparoscopic repair. RESULTS: A 75-year-old woman with a history of low back and left lower extremity pain with radiographic evidence of foraminal stenosis and degenerative spondylolisthesis underwent a successful L4-L5 discectomy with an extreme lateral interbody fusion via a retroperitoneal transpsoas approach. This was supplemented with a posterior minimally invasive surgery instrumented fusion from L4 to L5. The patient reported significant improvement in symptoms on initial follow-up, however, complained of a prominence over her incision 4 weeks later. An incisional hernia was diagnosed and subsequently repaired laparoscopically, from which the patient recovered uneventfully. CONCLUSIONS: Postoperative incisional hernia after extreme lateral interbody fusion is a complication that has not been previously described in the literature but is one that spine surgeons must recognize. This case may prompt surgeons to use a more posterior approach to avoid this complication. Additionally, direct repair of the transversalis fascia is critical to avoiding this complication.

Unilateral vs bilateral total knee arthroplasty risk factors increasing morbidity.

Because surgeons are electing to perform simultaneous bilateral total knee arthroplasty (TKA), it is important to identify which patients are at increased risk. We performed a retrospective cohort analysis of 150 patients with unilateral TKA vs 150 patients with simultaneous bilateral TKA. The bilateral group demonstrated a 2.1 times greater mean overall complication rate as well as increased transfusion rates. Patients older than 70 years exhibited significantly higher complication rates. Having a preexisting pulmonary disorder in the bilateral cohort carried nearly a 3-fold risk of complications. Patients with body mass indices greater than 30 displayed a complication rate of 0.97 in the bilateral group as opposed to 0.44 in the control group. Our study demonstrated that age, body mass index, and a preexisting pulmonary disorder resulted in increased complications.

Influence of stem size on clinical outcome of primary total hip arthroplasty with cementless extensively porous-coated femoral components.

This study retrospectively evaluated the clinical outcome of primary total hip arthroplasty as a function of stem diameter in 1545 patients implanted with extensively porous-coated stems. Less than 2% of femoral components were loose or revised; femoral survivorship was 97.9% at 15 years. Of patients with stable components, 95 to 97% had increased function, decreased pain, and overall satisfaction. Although 17% of patients indicated activity-limiting pain, only 3% were dissatisfied with the results of their hip arthroplasty. Logistic regression demonstrated no statistical relationship between stem size and either revision, loosening, pain, or satisfaction. We conclude that patients with large-diameter, extensively porous-coated femoral components are no more likely to be revised, loose, or have thigh or activity-limiting pain than patients with smaller diameter stems.