Augmented Reality-Guided Mastoidectomy Simulation: A Randomized Controlled Trial Assessing Surgical Proficiency.

OBJECTIVE: Mastoidectomy surgical training is challenging due to the complex nature of the anatomical structures involved. Traditional training methods based on direct patient care and cadaveric temporal bone training have practical shortcomings. 3D-printed temporal bone models and augmented reality (AR) have emerged as promising solutions, particularly for mastoidectomy surgery, which demands an understanding of intricate anatomical structures. Evidence is needed to explore the potential of AR technology in addressing these training challenges. METHODS: 21 medical students in their clinical clerkship were recruited for this prospective, randomized controlled trial assessing mastoidectomy skills. The participants were randomly assigned to the AR group, which received real-time guidance during drilling on 3D-printed temporal bone models, or to the control group, which received traditional training methods. Skills were assessed on a modified Welling scale and evaluated independently by two senior otologists. RESULTS: The AR group outperformed the control group, with a mean overall drilling score of 19.5 out of 25, compared with the control group's score of 12 (p < 0.01). The AR group was significantly better at defining mastoidectomy margins (p < 0.01), exposing the antrum, preserving the lateral semicircular canal (p < 0.05), sharpening the sinodural angle (p < 0.01), exposing the tegmen and attic, preserving the ossicles (p < 0.01), and thinning and preserving the external auditory canal (p < 0.05). CONCLUSION: AR simulation in mastoidectomy, even in a single session, improved the proficiency of novice surgeons compared with traditional methods. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Virtual Reality-Enhanced Assessment of the Anterior Glottic Angle Using Cadaveric Models: A Proof-of-Concept Study.

OBJECTIVES: Vocal fold paralysis (VFP) is a complex disorder that affects voice, speech, swallowing, and overall quality of life. Current evaluation methods for determining the position of paralyzed vocal folds lack the objectivity required for personalized interventions and research on innovative treatments for VFP. This study was designed to validate the accuracy and reproducibility of a virtual reality (VR)-based platform to measure the anterior glottic angle (AGA), a critical component in determining the position of a paralyzed vocal fold. STUDY DESIGN: Retrospective. METHODS: A retrospective analysis of computed tomography (CT) scans of 39 adult patients was conducted to measure the AGA shortly after death. Two measurement methods were used: 2-dimensional (2D)-CT for direct measurements on 2D images and a 3-dimensional (3D)-VR method utilizing a dedicated platform to create a 3D VR model of the larynx. The AGA measurements conducted by two senior otolaryngologists using the 3D-VR method were compared to the 2D-CT measurements made by one of these same otolaryngologists. RESULTS: The mean AGA measured by the 3D-VR method was found to be 32.936 ± 6.486° (n = 39), and the measurements were highly correlated (r = 0.9670, P < 0.0001). By contrast, the 2D-CT method without VR yielded a significantly lower mean angle of 23.754° (n = 35) with a higher standard deviation of 10.365°. The 3D-VR method demonstrated excellent reliability for AGA measurements (intraclass correlation coefficient of 0.954). CONCLUSION: The findings underscore the potential value of using a VR-based platform to improve reproducibility and reduce the variability in measurements of AGA in cases of VFP.

Virtual Reality Helps Describe the Progression of Thyroid Cartilage Calcification.

OBJECTIVES: Thyroid cartilage (TC) calcifications may impact surgical planning and clinical management. However, few studies to date have implemented virtual reality (VR) to evaluate these calcifications. This study assessed the feasibility of evaluating TC calcifications in various regions and measuring their volumes through VR models generated from computed tomography scans. We also investigated age and gender-related differences in calcification patterns. METHODS: Ninety-two participants were categorized into younger, middle-aged, and older age groups. Calcification patterns (degree in Hounsfield units and volume of calcification in cm3) in different TC regions were identified by VR analysis, which enabled comparisons between age groups and genders. RESULTS: Significant differences in calcification patterns were observed between males and females, particularly in the middle right, middle left, bottom left, and vertex regions. Age-related differences in the vertex region showed increased calcification in the older age group. CONCLUSION: This study points to the contribution of VR in the evaluation of complex anatomical structures. The findings revealed significant gender and age patterns in TC calcification. These insights can inform surgical planning and highlight the potential of using VR to gain a better understanding of TC calcification clinically.

Current state of the art and future directions for implantable sensors in medical technology: Clinical needs and engineering challenges.

Implantable sensors have revolutionized the way we monitor biophysical and biochemical parameters by enabling real-time closed-loop intervention or therapy. These technologies align with the new era of healthcare known as healthcare 5.0, which encompasses smart disease control and detection, virtual care, intelligent health management, smart monitoring, and decision-making. This review explores the diverse biomedical applications of implantable temperature, mechanical, electrophysiological, optical, and electrochemical sensors. We delve into the engineering principles that serve as the foundation for their development. We also address the challenges faced by researchers and designers in bridging the gap between implantable sensor research and their clinical adoption by emphasizing the importance of careful consideration of clinical requirements and engineering challenges. We highlight the need for future research to explore issues such as long-term performance, biocompatibility, and power sources, as well as the potential for implantable sensors to transform healthcare across multiple disciplines. It is evident that implantable sensors have immense potential in the field of medical technology. However, the gap between research and clinical adoption remains wide, and there are still major obstacles to overcome before they can become a widely adopted part of medical practice.

Virtual reality-based training and pre-operative planning for head and neck sentinel lymph node biopsy.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) is crucial for managing head and neck skin cancer. However, variable lymphatic drainage can complicate SLN detection when using Single-Photon Emission Computed Tomography (SPECT) or lymphoscintigraphy. Virtual Reality (VR) can contribute to pre-operative planning by simulating a realistic 3D model, which improves orientation. VR can also facilitate real-patient training outside the operating room. This study explored using a VR platform for pre-operative planning in head and neck skin cancer patients undergoing SLNBs and assessed its value for residential training. MATERIALS AND METHODS: In this prospective technology pilot study, attending surgeons and residents who performed 21 SLNB operations on patients with head and neck skin cancers (81% males, mean age 69.2 ± 11.3) used a VR simulation model based on each patient's pre-operative SPECT scan to examine patient-specific anatomy. After surgery, they completed a questionnaire on the efficiency of the VR simulation as a pre-operative planning tool and training device for residents. RESULTS: The attending surgeons rated the VR model's accuracy at 8.3 ± 1.6 out of 10. Three-quarters (76%) of residents reported increased confidence after using VR. The physicians rated the platform's contribution to residents' training at 7.4 ± 2.1 to 8.9 ± 1.3 out of 10. CONCLUSION: A VR SLNB simulation can accurately portray marked sentinel lymph nodes. It was rated high as a surgical planning and teaching tool among attending surgeons and residents alike and may play a role in pre-operative planning and resident training. Further studies are needed to explore its applications in practice.

Long-term safety of medical cannabis in Parkinson's disease: A retrospective case-control study.

BACKGROUND: Whole-plant medical cannabis (MC) products are widely used for controlling symptoms associated with Parkinson's disease (PD). Despite its widespread use, few studies have investigated the long-term impact of MC on the progression of PD or its safety profile. This study examined the effects of MC on PD in a real-life setting. METHODS: A retrospective case-control study of 152 idiopathic PD patients (mean age 69.1 ± 9.0 years), followed at the Sheba Medical Center Movement Disorders Institute (SMDI) from 2008 to 2022 was conducted. Seventy-six patients who used licensed whole-plant medical cannabis (MC) for at least a year were compared to a matched group who did not receive MC in terms of their Levodopa Equivalent Daily Dose (LEDD), Hoehn and Yahr (H&Y) stage, and cognitive, depressive, and psychotic symptoms. RESULTS: The median monthly dose of MC was 20 g (IQR: 20-30), with a median Tetrahydrocannabinol (THC) percentage of 10 (IQR: 9.5-14.15) and a median Cannabidiol (CBD) percentage of 4 (IQR: 2-10). There were no significant differences between the MC and the control groups for LEDD or H&Y stage progression (p = 0.90, 0.77, respectively). A Kaplan-Meier analysis showed no evidence of relative worsening of psychotic, depressive, or cognitive symptoms reported by patients to their treating physicians over time in the MC group (p = 0.16-0.50). CONCLUSION: Over the 1-3 years of follow-ups, the MC treatment regimens appeared to be safe. MC did not exacerbate neuropsychiatric symptoms and had no detrimental effects on disease progression.

Autoimmune disorders caused by intravesical bacillus Calmette-Guerine treatment: A systematic review.

Intravesical bacillus Calmette-Guérin (BCG) is a common and highly effective treatment for non-muscle invasive urothelial carcinoma of the urinary bladder. BCG may cause an autoimmune reaction in some patients. One hundred and fifty-eight papers were analyzed, for a total of hundred and thirty patients with reactive arthritis, sixty patients with ocular manifestations and eighteen patients with other rheumatologic diseases. Among 130 subjects with reactive arthritis, an autoimmune symptom occurred after 5 instillations of intravesical BCG (IQR 4-6), which represents 5 weeks in most cases. Fifty-one patients had concurrent ocular involvement. The resolution of symptoms was achieved in a median of 32.5 days (IQR 14-90). Forty-two men and twenty women had ocular manifestations, most commonly conjunctivitis. Patients with HLA-B27 typing had earlier presentation of ocular symptoms related to the number of instillations (4.5 vs 6 [p < 0.05]. Resolution of symptoms was achieved at a median of 128 days (IQR 21-150). Among patients treated with NSAIDs (either with or without steroids), the duration of the disease was significantly shorter in both the articular and the ocular groups (28 vs. 120 [p < 0.05] and 30 vs.105 [p < 0.05], respectively). Other autoimmune manifestations included general autoimmune diseases, such as vasculitis, psoriasis and myasthenia gravis.

Virtual reality utilization for left atrial appendage occluder device size prediction.

Aim: To explore the feasibility and accuracy of virtual reality (VR) derived from cardiac computed angiography (CCTA) data to predict left atrial appendage occlusion (LAAO) device size. Method: Retrospective data of patients who underwent LAAO according to clinical indication were reviewed; all patients underwent a pre-procedural CCTA. Measurements of the left atrial appendage (LAA) orifice diameters by CCTA, VR, and transesophageal echocardiography (TEE) (acquired during the procedure) were compared to the implanted device size. The LAA perimeter was calculated using the Ramanujan approximation. Statistical analyses included Lin's Concordance Correlation Coefficient (ρ c ), the mean difference, and the mean square error (MSE). Results: The sample was composed of 20 patients (mean age 75.7 ± 7.5 years, 60% males) who underwent successful LAAO insertion (ACP™ N = 8, Watchman™ N = 12). The CCTA, VR, and TEE maximal diameter ρ c was 0.52, 0.78 and 0.60, respectively with mean differences of +0.92 ± 4.0 mm, -1.12 ± 2.3 mm, and -3.45 ± 2.69 mm, respectively. The CCTA, VR, and TEE perimeter calculations ρ c were 0.49, 0.54, and 0.39 respectively with mean differences of +4.69 ± 11.5 mm, -9.88 ± 8.0 mm, and -16.79 ± 7.8 respectively. Discussion: A VR visualization of the LAA ostium in different perspectives allows for a better understanding of its funnel-shaped structure. VR measurement of the maximal ostium diameter had the strongest correlation with the diameter of the inserted device. VR may thus provide new imaging possibilities for the evaluation of complex pre-procedural structures such as the LAA.

Proof of concept: Comparative accuracy of semiautomated VR modeling for volumetric analysis of the heart ventricles.

Introduction: Simpson's rule is generally used to estimate cardiac volumes. By contrast, modern methods such as Virtual Reality (VR) utilize mesh modeling to present the object's surface spatial structure, thus enabling intricate volumetric calculations. In this study, two types of semiautomated VR models for cardiac volumetric analysis were compared to the standard Philips dedicated cardiac imaging platform (PDP) which is based on Simpson's rule calculations. Methods: This retrospective report examined the cardiac computed tomography angiography (CCTA) of twenty patients with atrial fibrillation obtained prior to a left atrial appendage occlusion procedure. We employed two VR models to evaluate each CCTA and compared them to the PDP: a VR model with Philips-similar segmentations (VR-PS) that included the trabeculae and the papillary muscles within the luminal volume, and a VR model that only included the inner blood pool (VR-IBP). Results: Comparison of the VR-PS and the PDP left ventricle (LV) volumes demonstrated excellent correlation with a ρ c of 0.983 (95% CI 0.96, 0.99), and a small mean difference and range. The calculated volumes of the right ventricle (RV) had a somewhat lower correlation of 0.89 (95% CI 0.781, 0.95), a small mean difference, and a broader range. The VR-IBP chamber size estimations were significantly smaller than the estimates based on the PDP. Discussion: Simpson's rule and polygon summation algorithms produce similar results in normal morphological LVs. However, this correlation failed to emerge when applied to RVs and irregular chambers. Conclusions: The findings suggest that the polygon summation method is preferable for RV and irregular LV volume and function calculations.

Mycoplasma gallisepticum in vivo induced antigens expressed during infection in chickens.

Until now only a few genes encoding virulence factors have been characterized in the avian pathogen Mycoplasma gallisepticum. In order to identify candidate targets associated with infection we applied an immunoscreening technique-in vivo induced antigen technology (IVIAT)-to detect immunogens of M. gallisepticum strain Rlow expressed preferentially during in vivo infection. We identified 13 in vivo-induced (IVI) proteins that correspond to different functional categories including: previously reported putative virulence factors (GapA, PlpA, Hlp3, VlhA 1.07 and VlhA 4.01), transport (PotE, MGA_0241 and 0654), translation (L2, L23, ValS), chaperone (GroEL) and a protein with unknown function (MGA_0042). To validate the in vivo antigenic reactivity, 10 IVI proteins were tested by Western blot analysis using serum samples collected from chickens experimentally (with strain Rlow) and naturally (outbreaks, N=3) infected with M. gallisepticum. All IVI proteins tested were immunogenic. To corroborate these results, we tested expression of IVI genes in chickens experimentally infected with M. gallisepticum Rlow, and in MRC-5 human lung fibroblasts cell culture by using relative real time reverse-transcription PCR (RT-PCR). With the exception of MGA_0338, all six genes tested (MGA_1199, 0042, 0654, 0712, 0928 and 0241) were upregulated at least at one time point during experimental infection (2-4 week post-infection). In contrast, the expression of seven out of eight IVI genes (MGA_1199, 0152, 0338, 0042, 0654, 0712, 0928) were downregulated in MRC-5 cell culture at both 2 and 4h PI; MGA_0241 was upregulated 2h PI. Our data suggest that the identified IVI antigens may have important roles in the pathogenesis of M. gallisepticum infection in vivo.

Acquired resistance to the 16-membered macrolides tylosin and tilmicosin by Mycoplasma bovis.

The molecular mechanism of acquired resistance to the 16-membered macrolides tylosin (Ty) and tilmicosin (Tm) was investigated in Mycoplasma bovis field isolates. Sequence analysis of domains II and V of the two 23S rRNA alleles and ribosomal proteins L4 and L22 was performed on 54 M. bovis isolates showing different minimal inhibitory concentrations (MIC). The presence of any one of the point mutations G748A, C752T, A2058G, A2059G or A2059C (Escherichia coli numbering) in one or both alleles of the 23S rRNAs was correlated with decreased susceptibility to Ty (8-1024 µg/ml) and to Tm (32 to >256 µg/ml) in 27/27 and 27/31 M. bovis isolates, respectively. Although a single mutation in domain II or V could be sufficient to cause decreased susceptibility to Ty, our data imply that a combination of mutations in two domains is necessary to achieve higher MICs (≥ 128 µg/ml). The influence of a combination of mutations in two domains II and V on enhancement of resistance to Tm was less clear. In addition, the amino acid (aa) substitution L22-Q90H was found in 24/32 representative M. bovis isolates with different MICs, but no correlation with decreased susceptibility to Ty or Tm was identified. Multiple aa substitutions were also identified in the L4 protein, including at positions 185-186 (positions 64 and 65 in E. coli) which are adjacent to the macrolide-binding site. This is the first description of the molecular mechanism of acquired resistance to the 16-membered macrolides in M. bovis.

Molecular characterization of newly identified IS3, IS4 and IS30 insertion sequence-like elements in Mycoplasma bovis and their possible roles in genome plasticity.

Insertion sequences (ISs) are mobile genetic elements widely distributed among bacteria. Their impact on the bacterial genome is multifold, including transfer of genetic information, shuttle of adaptive traits and influence on the genomic content. As a result, ISs play an important role in the organization, plasticity and evolution of bacterial genomes. In this study, four new IS elements: ISMbov7; ISMbov4 and ISMbov5; and ISMbov6, related, respectively, to the IS3, IS4 and IS30 gene families, were identified and characterized with respect to inverted repeat (IR) and directly repeated (DR) sequences, putative target specificity and motifs related to transposase function. For instance, IS30-related ISMbov6 isoform elements were shown to (1) contain an alpha-helix-turn-alpha-helix homeodomain (HTH), (2) generate long DR and (3) possess target specificity for a palindromic sequence derived from putative rho-independent transcription terminators. Members of the IS3 family, which had not been documented previously in Mycoplasma bovis, contain HTH, leucine zipper and AT-hook motifs, which may be involved in DNA binding. In addition, the availability of the M. bovis PG45 genome sequence allowed us to elucidate the genomic organization of 54 intact or truncated IS elements and their possible effect on the expression of adjacent genes.

Molecular characterization of the Mycoplasma bovis p68 gene, encoding a basic membrane protein with homology to P48 of Mycoplasma agalactiae.

Mycoplasmal lipoproteins are considered to be potential virulence determinants, which may carry out numerous important functions in pathogenesis including adhesion and immunomodulation. The prototype mycoplasmal immunomodulin is the macrophage-activating lipoprotein (MALP) of Mycoplasma fermentans. In this study, a homolog of the malp gene, designated p68, was identified and characterized in Mycoplasma bovis strain PG45 clonal variant #6. P68 belongs to the family of basic membrane proteins, which have been identified in diverse prokaryotes, including mycoplasmas. P68 revealed significant similarity and shared conserved selective lipoprotein-associated motifs with the highly immunogenic MALP-related lipoproteins P48 of M. bovis and P48 of Mycoplasma agalactiae. Determination of the genomic distribution of both M. bovis malp-homologs showed that p48 was present in all M. bovis strains tested, whereas the p68 gene was missing in some. Sequence comparison of the p68 genomic region in strains with and without this gene revealed that the region is very dynamic, with multiple genetic changes. Reverse-transcription PCR and primer extension analysis indicated that both p68 and p48 are transcribed in M. bovis under in vitro growth conditions. Mycoplasma bovis is the first mycoplasma species in which two malp-related genes have been identified.

Identification and characterization of phytoplasmal genes, employing a novel method of isolating phytoplasmal genomic DNA.

Phytoplasmas are unculturable, insect-transmissible plant pathogens belonging to the class Mollicutes. To be transmitted, the phytoplasmas replicate in the insect body and are delivered to the insect's salivary glands, from where they are injected into the recipient plant. Because phytoplasmas cannot be cultured, any attempt to recover phytoplasmal DNA from infected plants or insects has resulted in preparations with a large background of host DNA. Thus, studies of the phytoplasmal genome have been greatly hampered, and aside from the rRNA genes, only a few genes have hitherto been isolated and characterized. We developed a unique method to obtain host-free phytoplasmal genomic DNA from the insect vector's saliva, and we demonstrated the feasibility of this method by isolating and characterizing 78 new putative phytoplasmal open reading frames and their deduced proteins. Based on the newly accumulated information on phytoplasmal genes, preliminary characteristics of the phytoplasmal genome are discussed.

Cytadherence-deficient mutants of Mycoplasma gallisepticum generated by transposon mutagenesis.

Cytadherence-related molecules of Mycoplasma gallisepticum strain R-low were identified by Tn4001 transposon mutagenesis with the hemadsorption (HA) assay as an indicator for cytadherence. Three Gm(r) HA-negative (HA(-)) colonies displaying a stable HA(-) phenotype through several successive generations in which gentamicin selection was maintained were isolated from four independent transformation experiments and characterized. Southern blot analysis showed that the transposon was inserted as a single copy within the genome of each of the HA(-) mutants, suggesting that the transposon insertion was directly responsible for their inability to attach to erythrocytes. Sequence analysis of the transposon insertion sites revealed that in two mutants, the transposon was inserted at two distinct sites within the gapA structural gene. In the third mutant, the insertion was mapped within the crmA gene, which is located immediately downstream of the gapA gene as part of the same operon. In vitro attachment experiments with the MRC-5 human lung fibroblast cell line showed that the cytadherence capabilities of the HA(-) mutants were less than 25% those of original strain R. Experimental infection of chickens, the natural host of M. gallisepticum, with each of the three mutants demonstrated significantly impaired colonization and host responses. These data demonstrate conclusively the role of both GapA and CrmA proteins in the adherence of M. gallisepticum to host cells in model systems and in vivo colonization. Furthermore, these results underscore the relevance of in vitro cytadherence model systems for studying the pathogenesis of natural infections in chickens.

Variable lipoprotein genes of Mycoplasma agalactiae are activated in vivo by promoter addition via site-specific DNA inversions.

Mycoplasma agalactiae, the etiological agent of contagious agalactia of small ruminants, has a family of related genes (avg genes) which encode surface lipoprotein antigens that undergo phase variation. A series of 13 M. agalactiae clonal isolates, obtained from one chronically infected animal over a period of 7 months, were found to undergo major rearrangement events within the avg genomic locus. We show that these rearrangements regulate the phase-variable expression of individual avg genes. Northern blot analysis and reverse transcription-PCR showed that only one avg gene is transcribed, while the other avg genes are transcriptionally silent. Sequence analysis and primer extension experiments with two M. agalactiae clonal isolates showed that a specific 182-bp avg 5' upstream region (avg-B(2)) that is present as a single chromosomal copy serves as an active promoter and exhibits a high level of homology with the vsp promoter of the bovine pathogen Mycoplasma bovis. PCR analysis showed that each avg gene is associated with the avg-B(2) promoter in a subpopulation of cells that is present in each subclone. Multiple sequence-specific sites for DNA recombination (vis-like), which are presumably recognized by site-specific recombinase, were identified within the conserved avg 5' upstream regions of all avg genes and were found to be identical to the recombination sites of the M. bovis vsp locus. In addition, a gene encoding a member of the integrase family of tyrosine site-specific recombinases was identified adjacent to the variable avg locus. The molecular genetic basis for avg phase-variable expression appears to be mediated by site-specific DNA inversions occurring in vivo that allow activation of a silent avg gene by promoter addition. A model for the control of avg genes is proposed.

Identification and characterization of a site-specific tyrosine recombinase within the variable loci of Mycoplasma bovis, Mycoplasma pulmonis and Mycoplasma agalactiae.

Three highly mutable loci of the wall-less pathogens Mycoplasma bovis, Mycoplasma pulmonis and Mycoplasma agalactiae undergo high-frequency genomic rearrangements and generate extensive antigenic variation of major surface lipoproteins. Adjacent to each locus, an open reading frame exists as a single chromosomal copy and is predicted to encode a site-specific DNA recombinase exhibiting high homology to the recombinases XerD of Escherichia coli and CodV of Bacillus subtilis. Each of the mycoplasmal proteins are members of the lambda integrase family of tyrosine site-specific recombinases and likely mediates site-specific DNA inversions observed within the adjacent, variable loci.

Extended repertoire of genes encoding variable surface lipoproteins in Mycoplasma bovis strains.

A genomic cluster of vsp genes was previously shown to mediate high-frequency phenotypic switching of surface lipoprotein antigens in the bovine pathogen Mycoplasma bovis. This study revealed that field strains of M. bovis possess modified versions of the vsp gene complex in which extensive sequence variations occur primarily in the reiterated coding sequences of the vsp structural genes. These findings demonstrate that there is a vastly expanded potential for antigenic variation within populations of this organism.