Prediction of heart transplant rejection from routine pathology slides with self-supervised deep learning.

Aims: One of the most important complications of heart transplantation is organ rejection, which is diagnosed on endomyocardial biopsies by pathologists. Computer-based systems could assist in the diagnostic process and potentially improve reproducibility. Here, we evaluated the feasibility of using deep learning in predicting the degree of cellular rejection from pathology slides as defined by the International Society for Heart and Lung Transplantation (ISHLT) grading system. Methods and results: We collected 1079 histopathology slides from 325 patients from three transplant centres in Germany. We trained an attention-based deep neural network to predict rejection in the primary cohort and evaluated its performance using cross-validation and by deploying it to three cohorts. For binary prediction (rejection yes/no), the mean area under the receiver operating curve (AUROC) was 0.849 in the cross-validated experiment and 0.734, 0.729, and 0.716 in external validation cohorts. For a prediction of the ISHLT grade (0R, 1R, 2/3R), AUROCs were 0.835, 0.633, and 0.905 in the cross-validated experiment and 0.764, 0.597, and 0.913; 0.631, 0.633, and 0.682; and 0.722, 0.601, and 0.805 in the validation cohorts, respectively. The predictions of the artificial intelligence model were interpretable by human experts and highlighted plausible morphological patterns. Conclusion: We conclude that artificial intelligence can detect patterns of cellular transplant rejection in routine pathology, even when trained on small cohorts.

Ultrastructural Evidence of Mitochondrial Dysfunction in Osteomyelitis Patients.

Osteomyelitis is a difficult-to-treat disease with high chronification rates. First studies suggest increases in mitochondrial fission and mitochondrial dysfunction as possible contributors to the accumulation of intracellular reactive oxygen species and thereby to the cell death of infected bone cells. The aim of the present study is to analyze the ultrastructural impact of bacterial infection on osteocytic and osteoblastic mitochondria. Human infected bone tissue samples were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their mitochondria were analyzed histomorphometrically and compared with the control group of noninfectious human bone tissue samples. The results depicted swollen hydropic mitochondria including depleted cristae and a decrease in matrix density in the infected samples. Furthermore, perinuclear clustering of mitochondria could also be observed regularly. Additionally, increases in relative mitochondrial area and number were found as a correlate for increased mitochondrial fission. In conclusion, mitochondrial morphology is altered during osteomyelitis in a comparable way to mitochondria from hypoxic tissues. This gives new perspectives on the treatment strategies since the manipulation of mitochondrial dynamics may improve bone cell survival as a potential new target for the therapy of osteomyelitis.

Structural Analysis of Mitochondrial Dynamics-From Cardiomyocytes to Osteoblasts: A Critical Review.

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.

Self in medicine: Determinants of physician well-being and future directions in improving wellness.

CONTEXT: Medicine, a profession dedicated to the wellness of patients, is struggling with a crisis of physician and trainee wellness. Physicians and trainees are burning out at alarming rates. Historically, medicine has been characterised by challenging working conditions and inattention to physician wellness and self-care. Healthy physicians are better at promoting wellness to their patients, and physicians who are suffering from burnout can deliver compromised patient care. DISCUSSION: In recent years, research has increasingly focused on the causes of unwellness among doctors, and a broad range of health determinants have been identified. Studies of interventions for improving trainee and physician wellness have identified individual-focused and organisational approaches that can address the root causes of burnout. Insights from the corporate workplace may help guide interventions. Strategies for addressing physician burnout and improving wellness will involve innovative and multifaceted approaches. Despite a growing emphasis of physician wellness in the literature, implementation of wellness interventions is lagging, and quality improvement methods can address these challenges. CONCLUSION: Physician wellness is a shared responsibility among doctors, health care organisations and governing bodies. Addressing burnout and improving physician wellness will require transformational change and the embracement of a culture of wellness in medicine. Quality improvement methods are the next step in identifying effective wellness interventions and the targeted groups of physicians and trainees who will most benefit.

Validation of oil fate and mass balance for the Deepwater Horizon oil spill: Evaluation of water column partitioning.

Model predictions of oil transport and fate for the 2010 Deepwater Horizon oil spill (Gulf of Mexico) were compared to field observations and absolute and relative concentrations of oil compounds in samples from 900 to 1400 m depth <11 km from the well. Chemical partitioning analyses using quantitative indices support a bimodal droplet size distribution model for oil released during subsea dispersant applications in June with 74% of the mass in >1 mm droplets that surfaced near the spill site within a few hours, and 1-8% as <0.13 mm microdroplets that remained below 900 m. Analyses focused on 900-1400 m depth <11 km from the well indicate there was substantial biodegradation of dissolved components, some biodegradation in microdroplets, recirculation of weathered microdroplets into the wellhead area, and marine oil snow settling from above 900 m carrying more-weathered particulate oil into the deep plume.

Intracellular S. aureus in Osteoblasts in a Clinical Sample from a Patient with Chronic Osteomyelitis-A Case Report.

The pathophysiological role of intracellular bacteria in osteomyelitis is still a matter of debate. Here, we demonstrate for the first time the presence of Staphylococcus aureus internalized into osteoblasts in human tissue samples of a case with a chronic osteomyelitis using ultrastructural transmission electron microscope analysis.

Oil fate and mass balance for the Deepwater Horizon oil spill.

Based on oil fate modeling of the Deepwater Horizon spill through August 2010, during June and July 2010, ~89% of the oil surfaced, ~5% entered (by dissolving or as microdroplets) the deep plume (>900 m), and ~6% dissolved and biodegraded between 900 m and 40 m. Subsea dispersant application reduced surfacing oil by ~7% and evaporation of volatiles by ~26%. By July 2011, of the total oil, ~41% evaporated, ~15% was ashore and in nearshore (<10 m) sediments, ~3% was removed by responders, ~38.4% was in the water column (partially degraded; 29% shallower and 9.4% deeper than 40 m), and ~2.6% sedimented in waters >10 m (including 1.5% after August 2010). Volatile and soluble fractions that did not evaporate biodegraded by the end of August 2010, leaving residual oil to disperse and potentially settle. Model estimates were validated by comparison to field observations of floating oil and atmospheric emissions.

Impact of work hours and sleep on well-being and burnout for physicians-in-training: the Resident Activity Tracker Evaluation Study.

OBJECTIVE: The Resident Activity Tracker Evaluation (RATE) is a prospective observational study evaluating the impact of work hours, sleep and physical activity on resident well-being, burnout and job satisfaction. BACKGROUND: Physician burnout is common and its incidence is increasing. The impact of work hours and sleep on resident well-being and burnout remains elusive. Activity trackers are an innovative tool for measuring sleep and physical activity. METHODS: Residents were recruited from (i) general surgery and orthopaedics (SURG), (ii) internal medicine and neurology (MED) and (iii) anaesthesia and radiology (RCD). Groups 1 and 2 do not enforce restrictions on the duration of being on-call, and group 3 had restricted the duration of being on-call to 12 hours. Participants wore FitBit trackers for 14 days. Total hours worked, daily sleep, sleep on-call and daily steps were recorded. Participants completed validated surveys assessing self-reported well-being (Short-Form Health Survey), burnout (Maslach Burnout Inventory), and satisfaction with medicine. RESULTS: Surgical residents worked the most hours per week, followed by medical and RCD residents (SURG, 84.3 hours, 95% CI, 80.2-88.5; MED, 69.2 hours, 95% CI, 65.3-73.2; RCD, 52.2 hours, 95% CI, 48.2-56.1; p < 0.001). Surgical residents obtained fewer hours of sleep per day (SURG, 5.9 hours, 95% CI, 5.5-6.3; MED, 6.9 hours, 95% CI, 6.5-7.3; RCD, 6.8 hours, 95% CI, 5.6-7.2; p < 0.001). Nearly two-thirds of participants (61%) scored high burnout on the Maslach depersonalisation subscore. Total steps per day and well-being, burnout and job satisfaction were comparable between groups. Total hours worked, daily sleep and steps per day did not predict burnout or well-being. CONCLUSIONS: Work hours and average daily sleep did not affect burnout. Physical activity did not prevent burnout. Work hour restrictions may lead to increased sleep but may not affect resident burnout or well-being.

Application of an Integrated Blowout Model System, OILMAP DEEP, to the Deepwater Horizon (DWH) Spill.

OILMAP DEEP, an integrated system of models (pipeline release, blowout plume, dispersant treatment, oil droplet size distribution, and fountain and intrusion), was applied to the Deepwater Horizon (DWH) oil spill to predict the near field transport and fate of the oil and gas released into the northeastern Gulf of Mexico. The model included multiple, time dependent releases from both the kink and riser, with the observed subsurface dispersant treatment, that characterized the DWH spill and response. The blowout model predictions are in good agreement with the available observations for plume trapping height and the major characteristics of the intrusion layer. Predictions of the droplet size distribution are in good agreement with the limited in situ Holocam observations. Model predictions of the percentage of oil retained in the intrusion layer are consistent with independent estimates based on field observations.

Ipsilateral Motor Innervation Discovered Incidentally on Intraoperative Monitoring: A Case Report.

Background and importance: Lesions in the corticospinal tract above the decussation at the medullary pyramids almost universally produce contralateral deficits. Rare cases of supratentorial lesions causing ipsilateral motor deficits have been reported previously, but only ever found secondary to stroke or congenital pyramidal tract malformations. Clinical presentation: Herein, we report a case of ipsilateral corticospinal tract innervation discovered incidentally with intraoperative monitoring during a microsurgical resection of a vestibular schwannoma. Intraoperative monitoring with electrical transcranial stimulation of the frontal scalp triggered motor-evoked potentials in the ipsilateral arms. The uncrossed pathways were later confirmed with MRI tractography using diffusion tensor imaging. Conclusion: To the best of our knowledge, this is the first case of isolated ipsilateral motor innervation of the corticospinal tract discovered incidentally during a neurosurgical procedure. Given the increasing use of intraoperative monitoring, this case underscores the importance of cautious interpretation of seemingly discordant neurophysiological findings. Once technical issues have been ruled out, ipsilateral motor innervation may be considered as a possible explanation and neurosurgeons should be aware of the existence of this rare anatomic variant.

Clinical and Radiographic Factors Predicting Hearing Preservation Rates in Large Vestibular Schwannomas.

Objectives Postoperative hearing preservation rates for patients with large vestibular schwannomas range from 0 to 43%. The clinical and radiographic factors predicting hearing preservation in smaller vestibular schwannomas are well described; however, their importance in larger tumors is unclear. We investigated factors predicting hearing preservation in large vestibular schwannomas. Design Retrospective review. Setting Quaternary care academic center. Participants A total of 85 patients with unilateral vestibular schwannomas > 3 cm underwent retrosigmoid resections. Main Outcomes Measures Preoperative and postoperative serviceable hearing rates. Methods Clinical and radiographic data including preoperative and postoperative audiograms, preoperative symptoms, magnetic resonance imaging features, and postoperative facial weakness were analyzed. Results Hearing was preserved in 41% of patients (17 of 42) with preoperative serviceable hearing. Hypertension and diabetes increased the likelihood of preoperative hearing loss. Preoperative tinnitus predicted a lower likelihood of hearing preservation. No radiographic factors predicted hearing preservation; however, larger tumor size, smaller fourth ventricular width, and the presence of a cerebrospinal fluid cleft surrounding the tumor predicted postoperative facial weakness. Conclusion Systemic comorbidities may influence hearing loss preoperatively in patients with large vestibular schwannomas. The absence of tinnitus may reflect hearing reserve and propensity for hearing preservation. Preoperative radiographic features did not predict hearing preservation despite some associations with postoperative facial weakness.

Economic evaluation comparing intraoperative cone beam CT-based navigation and conventional fluoroscopy for the placement of spinal pedicle screws: a patient-level data cost-effectiveness analysis.

BACKGROUND CONTEXT: Pedicle screws are routinely used in contemporary spinal surgery. Screw misplacement may be asymptomatic but is also correlated with potential adverse events. Computer-assisted surgery (CAS) has been associated with improved screw placement accuracy rates. However, this technology has substantial acquisition and maintenance costs. Despite its increasing usage, no rigorous full economic evaluation comparing this technology to current standard of care has been reported. PURPOSE: Medical costs are exploding in an unsustainable way. Health economic theory requires that medical equipment costs be compared with expected benefits. To answer this question for computer-assisted spinal surgery, we present an economic evaluation looking specifically at symptomatic misplaced screws leading to reoperation secondary to neurologic deficits or biomechanical concerns. STUDY DESIGN/SETTING: The study design was an observational case-control study from prospectively collected data of consecutive patients treated with the aid of CAS (treatment group) compared with a matched historical cohort of patients treated with conventional fluoroscopy (control group). PATIENT SAMPLE: The patient sample consisted of consecutive patients treated surgically at a quaternary academic center. OUTCOME MEASURES: The primary effectiveness measure studied was the number of reoperations for misplaced screws within 1 year of the index surgery. Secondary outcome measures included were total adverse event rate and postoperative computed tomography usage for pedicle screw examination. METHODS: A patient-level data cost-effectiveness analysis from the hospital perspective was conducted to determine the value of a navigation system coupled with intraoperative 3-D imaging (O-arm Imaging and the StealthStation S7 Navigation Systems, Medtronic, Louisville, CO, USA) in adult spinal surgery. The capital costs for both alternatives were reported as equivalent annual costs based on the annuitization of capital expenditures method using a 3% discount rate and a 7-year amortization period. Annual maintenance costs were also added. Finally, reoperation costs using a micro-costing approach were calculated for both groups. An incremental cost-effectiveness ratio was calculated and reported as cost per reoperation avoided. Based on reoperation costs in Canada and in the United States, a minimal caseload was calculated for the more expensive alternative to be cost saving. Sensitivity analyses were also conducted. RESULTS: A total of 5,132 pedicle screws were inserted in 502 patients during the study period: 2,682 screws in 253 patients in the treatment group and 2,450 screws in 249 patients in the control group. Overall accuracy rates were 95.2% for the treatment group and 86.9% for the control group. Within 1 year post treatment, two patients (0.8%) required a revision surgery in the treatment group compared with 15 patients (6%) in the control group. An incremental cost-effectiveness ratio of $15,961 per reoperation avoided was calculated for the CAS group. Based on a reoperation cost of $12,618, this new technology becomes cost saving for centers performing more than 254 instrumented spinal procedures per year. CONCLUSIONS: Computer-assisted spinal surgery has the potential to reduce reoperation rates and thus to have serious cost-effectiveness and policy implications. High acquisition and maintenance costs of this technology can be offset by equally high reoperation costs. Our cost-effectiveness analysis showed that for high-volume centers with a similar case complexity to the studied population, this technology is economically justified.

Patient and surgeon radiation exposure during spinal instrumentation using intraoperative computed tomography-based navigation.

BACKGROUND CONTEXT: Imaging modalities used to visualize spinal anatomy intraoperatively include X-ray studies, fluoroscopy, and computed tomography (CT). All of these emit ionizing radiation. PURPOSE: Radiation emitted to the patient and the surgical team when performing surgeries using intraoperative CT-based spine navigation was compared. STUDY DESIGN/SETTING: This is a retrospective cohort case-control study. PATIENT SAMPLE: Seventy-three patients underwent CT-navigated spinal instrumentation and 73 matched controls underwent spinal instrumentation with conventional fluoroscopy. OUTCOME MEASURES: Effective doses of radiation to the patient when the surgical team was inside and outside of the room were analyzed. The number of postoperative imaging investigations between navigated and non-navigated cases was compared. METHODS: Intraoperative X-ray imaging, fluoroscopy, and CT dosages were recorded and standardized to effective doses. The number of postoperative imaging investigations was compared with the matched cohort of surgical cases. A literature review identified historical radiation exposure values for fluoroscopic-guided spinal instrumentation. RESULTS: The 73 navigated operations involved an average of 5.44 levels of instrumentation. Thoracic and lumbar instrumentations had higher radiation emission from all modalities (CT, X-ray imaging, and fluoroscopy) compared with cervical cases (6.93 millisievert [mSv] vs. 2.34 mSv). Major deformity and degenerative cases involved more radiation emission than trauma or oncology cases (7.05 mSv vs. 4.20 mSv). On average, the total radiation dose to the patient was 8.7 times more than the radiation emitted when the surgical team was inside the operating room. Total radiation exposure to the patient was 2.77 times the values reported in the literature for thoracolumbar instrumentations performed without navigation. In comparison, the radiation emitted to the patient when the surgical team was inside the operating room was 2.50 lower than non-navigated thoracolumbar instrumentations. The average total radiation exposure to the patient was 5.69 mSv, a value less than a single routine lumbar CT scan (7.5 mSv). The average radiation exposure to the patient in the present study was approximately one quarter the recommended annual occupational radiation exposure. Navigation did not reduce the number of postoperative X-rays or CT scans obtained. CONCLUSIONS: Intraoperative CT navigation increases the radiation exposure to the patient and reduces the radiation exposure to the surgeon when compared with values reported in the literature. Intraoperative CT navigation improves the accuracy of spine instrumentation with acceptable patient radiation exposure and reduced surgical team exposure. Surgeons should be aware of the implications of radiation exposure to both the patient and the surgical team when using intraoperative CT navigation.

Bilateral Pedicle and Crossed Translaminar Screws in C2.

Multiple techniques exist for the fixation of C2, including axial pedicle screws and bilateral translaminar screws. We describe a novel method of incorporating both the translaminar and pedicle screws within C2 to improve fixation to the subaxial spine in patients requiring posterior cervical instrumentation for deformity correction or instability. We report three cases of patients with cervical spinal instability, who underwent cervical spine instrumentation for stabilization and/or deformity correction. Bilateral C2 pedicle screws were inserted, followed by bilateral crossed laminar screws. The instrumentation method successfully achieved fixation in all three patients. There were no immediate postoperative complications, and hardware positioning was satisfactory. Instrumenting C2 with translaminar and pedicle screws is technically feasible, and it may improve fixation to the subaxial spine in patients with poor bone quality or severe subaxial deformity, which require a stronger instrumentation construct.

The contemporary practice of psychiatric surgery: results from a global survey of functional neurosurgeons.

BACKGROUND: Interest in neurosurgery for psychiatric diseases (NPD) has grown globally. We previously reported the results of a survey of North American functional neurosurgeons that evaluated general attitudes towards NPD and the future directions of the field. OBJECTIVES: The purpose of this study was to expand on our previous work and obtain a snapshot in time of global attitudes towards NPD among practicing functional neurosurgeons. We measure general and regional trends in functional neurosurgery and focus specifically on surgery for mind and mood, while exploring the future prospects of the field. METHODS: We designed an online survey and distributed it electronically to 881 members of the following international organizations: World Society for Stereotactic and Functional Neurosurgery, European Society for Stereotactic and Functional Neurosurgery, Asian-Australasian Society for Stereotactic Functional Neurosurgery and the South and Latin American Society for Stereotactic and Functional Neurosurgery. Subsequent statistical and thematic analysis was performed on the data obtained. RESULTS: Of 881 surveys distributed, 106 were returned (12.8%). Eighty-two percent of functional neurosurgeon respondents were fellowship trained, with movement disorders and pain making up the majority of their practice. Psychiatric indications are the most frequently treated conditions for 34% of survey respondents, and over half of participants (51%) perform epilepsy surgery. Of the psychiatric conditions, obsessive-compulsive disorder and depression are the most common disorders treated. The majority of respondents (90%) felt optimistic about the future of NPD. Two thirds cited the reluctance of psychiatrists to refer patients as the greatest obstacle facing the field, and a majority reported that a cultural stigma surrounding psychiatric diseases exists in their community. In response to hypothetical situations involving cognitive and personality enhancement, opinions varied, but the majority opposed enhancement interventions. Regional variations were examined as well and uncovered distinct attitudinal differences depending on geographic location. CONCLUSIONS: Surgery for psychiatric conditions is an expanding field within functional neurosurgery. The opinions of international functional neurosurgeons were largely in line with those of their North American colleagues. Optimism regarding the future of NPD predominates, and future editions of this survey can be used to track the evolution of neurosurgeons' attitudes towards NPD and neuroenhancement.

Percutaneous trigeminal rhizotomy for facial pain secondary to head and neck malignancy.

BACKGROUND: Nearly 80% of patients with head and neck cancers experience facial pain related to their tumor or treatment. The majority obtain pain relief with appropriate medical treatment. Occasionally some remain refractory to all analgesics or cannot tolerate the accompanying side effects. They may benefit from surgical intervention. OBJECTIVES: We report a case of medically intractable facial pain secondary to squamous cell carcinoma of the tongue that was successfully treated with percutaneous trigeminal rhizotomy. METHODS: Percutaneous trigeminal radiofrequency rhizotomy involves thermoablation of the trigeminal nerve within Meckel's cave by an electrode inserted through the cheek and foramen ovale. RESULTS: Facial pain was successfully controlled postoperatively. DISCUSSION: Percutaneous trigeminal rhizotomy is a surgical option for managing nociceptive pain secondary to a head and neck malignancy. This technique, last reported in the literature almost 30 years ago, must not be forgotten by the next generation of oncologists, pain specialists, and neurosurgeons.