Development and Validation of a Machine Learning COVID-19 Veteran (COVet) Deterioration Risk Score.

BACKGROUND AND OBJECTIVE: To develop the COVid Veteran (COVet) score for clinical deterioration in Veterans hospitalized with COVID-19 and further validate this model in both Veteran and non-Veteran samples. No such score has been derived and validated while incorporating a Veteran sample. DERIVATION COHORT: Adults (age ≥ 18 yr) hospitalized outside the ICU with a diagnosis of COVID-19 for model development to the Veterans Health Administration (VHA) (n = 80 hospitals). VALIDATION COHORT: External validation occurred in a VHA cohort of 34 hospitals, as well as six non-Veteran health systems for further external validation (n = 21 hospitals) between 2020 and 2023. PREDICTION MODEL: eXtreme Gradient Boosting machine learning methods were used, and performance was assessed using the area under the receiver operating characteristic curve and compared with the National Early Warning Score (NEWS). The primary outcome was transfer to the ICU or death within 24 hours of each new variable observation. Model predictor variables included demographics, vital signs, structured flowsheet data, and laboratory values. RESULTS: A total of 96,908 admissions occurred during the study period, of which 59,897 were in the Veteran sample and 37,011 were in the non-Veteran sample. During external validation in the Veteran sample, the model demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.88. This was significantly higher than NEWS (0.79; p < 0.01). In the non-Veteran sample, the model also demonstrated excellent discrimination (0.86 vs. 0.79 for NEWS; p < 0.01). The top three variables of importance were eosinophil percentage, mean oxygen saturation in the prior 24-hour period, and worst mental status in the prior 24-hour period. CONCLUSIONS: We used machine learning methods to develop and validate a highly accurate early warning score in both Veterans and non-Veterans hospitalized with COVID-19. The model could lead to earlier identification and therapy, which may improve outcomes.

Characterization of peripheral hematopoietic stem cells and monocytes in Parkinson's disease.

BACKGROUND: Emerging evidence has highlighted the pivotal role of the immune system in neurodegenerative diseases. This study investigated the impact of progressive neurodegeneration on the differentiation and development of hematopoietic stem cells in the peripheral blood of Parkinson's patients. METHODS: A colony-forming cell assay was established to study hematopoietic stem cells from venous blood of Parkinson's patients, and flow cytometry was used to analyze the expression of chemokine receptors on monocytes. RESULTS: We demonstrate that there is strong upregulation in the percentage of monocyte precursors in the peripheral blood of Parkinson's patients and asymptomatic high-risk individuals. We identify the receptor CCR2 as undergoing strong upregulation on the surface of classical monocytes in Parkinson's patients. CONCLUSIONS: The association between blood cell development and progressive cell death in the brain of Parkinson's patients should be further investigated as a potential dynamic biomarker and indicator of disease progression.

National Early Warning Score Deployment in a Veterans Affairs Facility: A Quality Improvement Initiative and Analysis.

Early warning scores are algorithms designed to identify clinical deterioration. Current literature is predominantly in non-Veteran populations. Studies in Veterans are lacking. This study was a prospective quality improvement project deploying and assessing the National Early Warning Score (NEWS) at Kansas City VA Medical Center. Performance of NEWS was assessed as follows: discrimination for predicting a composite outcome of intensive care unit transfer or mortality within 24 hours via area under the receiver operating curve. A total of 4781 Veterans with 142 375 NEWS values were included. The NEWS area under the receiver operating curve for the composite outcome was 0.72 (95% CI, 0.71-0.74), indicating acceptable predictive accuracy. A NEWS of ≥7 was more likely associated with the composite outcome versus <7 (13.6% vs 0.8%; P < 0.001). This is one of the first studies to demonstrate successful deployment of NEWS in a Veteran population, with resultant important implications across the Veterans Health Administration.

Lactate influences the gene expression profile of human mesenchymal stem cells (hMSC) in a dose dependant manner.

BACKGROUND/AIMS: Wounds, especially non-healing wounds are characterized by elevated tissue lactate concentrations. Lactate is known for being able to stimulate collagen synthesis and vessel growth. Lately it has been shown that lactate, in vivo, plays an important role in homing of stem cells. With this work we aimed to show the influence of lactate on the gene expressionprofile of human mesenchymal stem cells (hMSC). MATERIALS AND METHODS: hMSCs were obtained from bone marrow and characterized with fluorescence-activated cell sorting (FACS) analysis. Subsequently the hMSCs were treated with either 0, 5, 10 and 15 mM lactate (pH 7,4) for 24 hours. RNA Isolation from stimulated hMSCs and controls was performed. The Microarray analysis was performed using AffymetrixHuGene 1.0 ST Gene Chip. Selected targets were subsequently analysed using quantitative real time PCR (RTq-PCR). RESULTS: We were able to show that lactate in moderate concentrations of 5 respectively 10 mM leads to an anti-inflammatory, anti-apoptotic but growth and proliferation promoting gene expression after 24 h. In contrast, high lactate concentrations of 15 mM leads to the opposed effect, namely promoting inflammation and apoptosis. Hypoxia induced genes did not show any significant regulation. Contrary to expectation, we were not able to show any significant regulation of candidates associated with glycolysis. CONCLUSION: We were able to show that lactate alters gene expression but does not change the cell phenotype, which might be helpful for further investigations of new treatment strategies for chronic non-healing wounds as well as tumor-therapy and neuronal plasticity.

Primary Lymphoma of the Distal Femur Presenting as Spontaneous Deep Vein Thrombosis and Knee Monoarthritis: A Case Report.

CASE: A 68-year-old man with a history of unprovoked deep vein thrombosis (DVT) presented with recurrent knee effusions after the initiation of anticoagulation. Radiographs showed soft-tissue swelling without a distinct skeletal lesion. Magnetic resonance imaging, however, showed a marrow-replacing process in the distal femur. Subsequent biopsy demonstrated B-cell lymphoma. CONCLUSION: This is a rare case of a primary lymphoma of bone mimicking synovial disease. It also highlights the fact that an unprovoked DVT may be a harbinger of an undiagnosed underlying malignancy.

Hyperoxic and hyperbaric-induced cardioprotection: role of nitric oxide synthase 3.

OBJECTIVE: The relative contributions of the fraction of inspired oxygen (FIO2) and atmospheric pressure (ATM) to cardioprotection are unknown. We determined whether the product of FIO2 x ATM (oxygen partial pressure) controls the extent of hyperoxic+hyperbaric-induced cardioprotection and involves activation of nitric oxide synthase (NOS). METHODS: Adult Sprague Dawley rats (n = 10/gp) were treated for 1 h with (1) normoxia+normobaria (21% O2 at 1 ATM), (2) hyperoxia+normobaria (100% O2 at 1 ATM), (3) normoxia+hyperbaria (21% O2 at 2 ATM) and (4) hyperoxia+hyperbaria (100% O2 at 2 ATM). RESULTS: Infarct size following 25 min ischemia and 180 min reperfusion was decreased following hyperoxia+normobaria and normoxia+hyperbaria compared with normoxia+normobaria and further decreased following hyperoxia+hyperbaria treatment. l-NAME (200 microM) reversed the cardioprotective effects of hyperoxia+hyperbaria. Nitrite plus nitrate content was increased 2.2-fold in rats treated with normoxia+hyperbaria and hyperoxia+hyperbaria. NOS3 protein increased 1.2-fold and association of hsp90 with NOS3 four-fold in hyperoxic+hyperbaric rats. CONCLUSIONS: Cardioprotection conferred by hyperoxia+hyperbaria is directly dependent on oxygen availability and mediated by NOS.

The prevalence of admission for sarcoma in the military health system during 2002-2003.

The etiology of sarcomas is not clear. Environmental exposures have been implicated as potential agents in the development of some sarcomas, but more research is needed. The military health system (MHS) may be able to provide population-based information regarding sarcomas. Discharge diagnoses for bone sarcoma and soft tissue sarcoma were searched within a large administrative database maintained by the U.S. military. There were > 200 cases of bone sarcoma and > 300 cases of soft tissue sarcoma during the 2-year study period of 2002-2003. The crude prevalence of admission for bone sarcoma within the MHS was 1.2 cases per 100,000 per year. The crude prevalence of admission for soft tissue sarcoma was 1.7 cases per 100,000 per year. These statistics suggest that the MHS may be used to test hypotheses regarding sarcoma epidemiological features, especially for studies that concern military-related exposures. However, nearly 70% of the military beneficiaries who were sarcoma patients were admitted to civilian hospitals, as opposed to military treatment facilities. Therefore, population-based studies of sarcoma patients in the MHS should seek means to capture data for patients who are treated outside military facilities. The database used for this study may provide important information regarding these patients. In addition, military health care planners may use the information from this study to develop referral strategies within the MHS.

An internet-based referral/consultation system for the U.S.-associated Pacific Islands: its contribution to orthopedic graduate medical education at Tripler Army Medical Center.

To evaluate the benefit of the Pacific Island Health Care Project (PIHCP) to our orthopedic graduate medical education program, we performed a retrospective review of our 8-year operative experience with patients referred through this program. Between July 1994 and June 2002, 69 patients underwent 79 orthopedic operative procedures. Patients were categorized by primary diagnosis, anatomic site involved, and surgical treatment rendered. Because many of the patients referred from the PIHCP with tumors were noted to have either unusually large lesions or advanced-stage disease, further analyses of tumor stage and pathologic grade were made. Seven of the 14 oncologic cases surgically treated in our department in the past 8 years were referrals from the PIHCP. Unique operative procedures performed for these tumor patients included one forequarter amputation, one hip disarticulation, one hemipelvectomy, two partial scapulectomies, and one distal ulna excision. We conclude that the PIHCP referrals provide an important and relatively unique contribution to the clinical and operative experience of our orthopedic residents. These patients from the Pacific basin also enhance our orthopedic graduate medical education program by exposing our residents to the special socioeconomic and cultural issues related to caring for people from developing insular countries.

To distract or not to distract: an algorithm for airway management in isolated Pierre Robin sequence.

Approaches advocated for treatment of airway obstruction among neonates with Pierre Robin sequence include positioning, tongue-lip adhesion, mandibular distraction, and tracheostomy, with no established guidelines regarding which modality is appropriate for a specific patient. This report proposes an algorithm for the management of neonatal upper airway obstruction among patients with isolated Pierre Robin sequence. Data for 21 patients with isolated Pierre Robin sequence who were treated by one surgeon during a 9-year period were reviewed. Eighteen patients presented during the first 1 week of life and three patients presented late, between 12 and 33 months of age. Follow-up periods ranged from 9 to 70 months (median, 33 months). Successful airway management was achieved with positioning alone for 10 patients, with tongue-lip adhesion for seven of nine patients, with tracheostomy for two patients, and with mandibular distraction for three patients. Changes in the maxillary-mandibular discrepancy were significant with natural mandibular growth during the first 1 year of life (p < 0.0001). Oromotor studies performed 3 months or more after tongue-lip adhesion reversal (n = 9) demonstrated no appreciable deficits in tongue function, relative to other children with cleft lips/palates. A multidisciplinary team should evaluate all patients with isolated Pierre Robin sequence, to fully assess the maxillary-mandibular relationship, anatomically define the site of airway obstruction, and identify feeding difficulties. Patients should be evaluated for episodes of desaturation occurring spontaneously, during feeding, or during sleeping. Patients with desaturation should be further evaluated with double endoscopy (nasoendoscopy and bronchoscopy). If the airway obstruction is localized to the tongue base alone and cannot be controlled with positioning, then tongue-lip adhesion is the initial treatment of choice, because such patients demonstrate significant mandibular growth during the first 1 year of life. Mandibular distraction among neonates is reserved for failures of tongue-lip adhesion in which isolated tongue-base airway obstruction is documented. Neither of the patients who experienced failure of tongue-lip adhesion in this series would have been a candidate for distraction with the algorithm presented. Avoiding routine neonatal distraction serves to avoid facial scarring, nerve and tooth bud injury, and potential disturbances of intrinsic mandibular growth. Patients with persistent respiratory difficulties beyond age 9 months require reevaluation for multiple sites of airway obstruction. Mandibular distraction may be one of several modalities required to avoid tracheostomy for such patients.

Tuberculous tenosynovitis of the tibialis anterior tendon: a case report.

Tuberculous tenosynovitis is an uncommon form of extrapulmonary tuberculosis occurring primarily in the hands and wrists with limited reports involving the lower extremities. We report a rare case of tuberculous tenosynovitis of the tibialis anterior tendon occurring in a 37-year-old Filipino male. The tendon was surgically debrided and the patient was given a six month course of antituberculin chemotherapy. At one year postoperatively, the patient has good function with no evidence of recurrence.

Subpectoral biceps tenodesis: an anatomic study and evaluation of at-risk structures.

BACKGROUND: The neurovascular structures of the proximal arm may be at risk for iatrogenic injury during open subpectoral biceps tenodesis (OSPBT). PURPOSE: To define the anatomic relationships and at-risk structures during OSPBT and to quantify the effect of arm rotation on the position of the musculocutaneous nerve. STUDY DESIGN: Descriptive laboratory study. METHODS: The OSPBT approach was performed in 17 unembalmed cadaveric upper extremities. The tenodesis site was inferior to the bicipital groove and positioned so the musculotendinous portion of the long head of the biceps rested at the inferior border of the pectoralis major. A meticulous dissection identified the brachial artery, deep brachial artery, cephalic vein, brachial vein, medial brachial cutaneous nerve, medial antebrachial cutaneous nerve, intercostal brachial cutaneous nerve, musculocutaneous nerve, axillary nerve, median nerve, and radial nerve. Superficial structures were measured from the superior and inferior aspects of the incision, and deep structures were measured from the tenodesis site and nearest retractor. The musculocutaneous nerve was measured with the arm in neutral, internal, and external rotation. RESULTS: The musculocutaneous nerve was 10.1 mm (range, 6-18 mm) medial to the tenodesis location and 2.9 mm (range, 1-6 mm) medial to the medially placed retractor in neutral arm position. The radial nerve and deep brachial artery were 7.4 mm (range, 2-12 mm) and 5.7 mm (range, 1-10 mm) deep to the medially placed retractor, respectively. With the arm internally rotated to 45°, the musculocutaneous nerve was 8.1 mm from the tenodesis site, compared with 19.4 mm with the arm 45° externally rotated (P = .009). The median nerve, brachial artery, and brachial vein were >2.5 cm from the tenodesis site and nearest retractor during deep dissection. CONCLUSION: The musculocutaneous nerve, radial nerve, and deep brachial artery are within 1 cm of the standard medial retractor. External rotation of the arm moves the musculocutaneous nerve 11.3 mm further away from the tenodesis site compared with the internally rotated position. CLINICAL RELEVANCE: The musculocutaneous nerve, radial nerve, and deep brachial artery course in close proximity to the operative field and are therefore at risk during OSPBT. Limiting the use of medial retraction and placement of the arm in an externally rotated position will minimize neurovascular injury.

A systematic process to prioritize prevention activities sustaining progress toward the reduction of military injuries.

BACKGROUND: To sustain progress toward injury reduction and other health promotion goals, public health organizations need a systematic approach based on data and an evaluation of existing scientific evidence on prevention. This paper describes a process and criteria developed to systematically and objectively define prevention program and policy priorities. METHODS: Military medical surveillance data were obtained and summarized, and a working group of epidemiology and injury experts was formed. After reviewing the available data, the working group used predefined criteria to score leading military unintentional injury causes on five main criteria that assessed factors contributing to program and policy success: (1) importance of the problem, (2) effectiveness of existing prevention strategies, (3) feasibility of establishing programs and policies, (4) timeliness of implementation and results, and (5) potential for evaluation. Injury problems were ranked by total median score. RESULTS: Causes with the highest total median scores were physical training (34 points), military parachuting (32 points), privately-owned vehicle crashes (31 points), sports (29 points), falls (27 points), and military vehicle crashes (27 points). CONCLUSIONS: Using a data-driven, criteria-based process, three injury causes (physical training, military parachuting, and privately owned-vehicle crashes) with the greatest potential for successful program and policy implementation were identified. Such information is useful for public health practitioners and policymakers who must prioritize among health problems that are competing for limited resources. The process and criteria could be adapted to systematically assess and prioritize health issues affecting other communities.

Real-time reverse transcriptase polymerase chain reaction: an improvement in detecting mRNA levels in mouse cranial tissue.

BACKGROUND: Quantitation of messenger RNA levels has traditionally been carried out by Northern blot analysis. While this is regarded as the standard method, it is time-consuming and requires large quantities of RNA. Reverse-transcriptase polymerase chain reaction is a semiquantitative method that has been used as a more rapid and sensitive alternative to Northern blotting. Real-time reverse-transcriptase polymerase chain reaction is a quantitative technique that is gaining widespread acceptance as a rapid and reliable way of quantifying mRNA. Since both techniques are currently being used to evaluate gene expression in the murine cranial suture model, the present study was performed to compare the sensitivity and variability of real-time to conventional reverse-transcriptase polymerase chain reaction in this model. METHODS: Mouse brain RNA was isolated and amplified using real-time and conventional methods. For the real-time method, a serial 10-fold dilution of RNA, ranging from 1 fg to 100 ng, was performed. For the conventional method, the minimum amount of RNA needed for consistent polymerase chain reaction amplification was determined. Transforming growth factor beta-1 and beta-actin RNA transcripts were measured using both techniques. RESULTS: One femtogram of RNA could be detected by the real-time method, although 10 fg were required to reliably detect differences; 500 ng of RNA was required for consistent polymerase chain reaction amplification using the conventional method. The variability of real-time reverse-transcriptase polymerase chain reaction when expressed as a coefficient of variation (SD as a percentage of the mean) ranged from 0.23 to 2.6 percent for all genes tested, as compared with 9 to 70 percent for conventional reverse-transcriptase polymerase chain reaction. CONCLUSIONS: Real-time reverse-transcriptase polymerase chain reaction was used successfully to detect mRNA from different mouse genes. The real-time method is much more sensitive in detecting small amounts of mRNA than both Northern blot analysis and conventional polymerase chain reaction. The variability of the real-time method is more than 10-fold lower compared with the conventional method performed in the authors' laboratory for all genes tested.

Airway management in patients with isolated Pierre Robin sequence during the first year of life.

Managing the airway of patients with Pierre Robin sequence is diagnostically and therapeutically challenging. Like many other pathologies, Pierre Robin sequence is best managed with a multidisciplinary team. Providing a comprehensive evaluation is important to detect patients who may have silent events during activities of early life. Children with airway obstruction should have a complete assessment to anatomically define the site of airway obstruction. Therefore, management options can be targeted to the specific deficiency. The present article outlines a treatment protocol for patients who present with isolated Pierre Robin sequence. The authors propose that initial diagnostic and therapeutic interventions remain relatively noninvasive. Using this protocol, more than 80% of patients with isolated Pierre Robin sequence who the authors have examined for airway obstruction in the neonatal period have been effectively treated with positioning or tongue-lip adhesion. While more aggressive and successful techniques have been reported, the authors have not found them necessary for the majority of patients with isolated Pierre Robin sequence. The following review details their approach to patients with Pierre Robin sequence.

Outcomes of tongue-lip adhesion for neonatal respiratory distress caused by Pierre Robin sequence.

Tongue-lip adhesion can be effective in relieving tongue-based airway obstruction in the neonatal period. However, longitudinal evaluation of these patients demonstrates they require additional procedures for ultimate control of their airway, feeding, and orthognathic relationship. Charts of patients with Pierre Robin sequence who underwent unsuccessful nonoperative treatment and tongue-lip adhesion procedures by the senior author between 1989 to 1999 were reviewed. In particular, secondary interventions were quantified and qualified to determine if tongue-lip adhesion was a definitive treatment of the pathology caused by this sequence. Eleven patients with ages ranging from 2 to 6 weeks underwent initial tongue-lip adhesion. Seven patients were syndromic (3 Stickler's, 1 Goldenhar's, 1 Fragile X, 1 Miller's, 1 chromosome 15 rearrangement), and four had isolated Pierre Robin sequence. Two patients had dehiscence of their initial repair within 2 weeks, for a primary surgical success rate of 82%, consistent with other published reports. A detailed follow-up of these patients revealed that 10 of 11 (91%) required additional intervention for airway or feeding issues. Of those requiring secondary intervention, an additional 1.9 secondary procedures were performed per patient to achieve control of the airway, feeding, and orthognathic problems. More than half of the patients needed gastrostomy tubes to overcome feeding difficulties. Five patients necessitated secondary surgery for recurrent airway obstruction within 4 months of the initial surgical treatment (four distractions and one repeat tongue-lip adhesion). Four others required distraction at an older age for orthognathic indications. Two patients were successfully treated with tongue-lip adhesion only. Tongue-lip adhesion has a high initial success rate for correction of neonatal airway obstruction. However, long-term follow-up indicates a high incidence of secondary intervention requirements. In retrospect, perhaps tongue-lip adhesion should be considered a temporizing procedure for most patients with Pierre Robin sequence.

Microfocal CT: a method for evaluating murine cranial sutures in situ.

INTRODUCTION: The murine model is a well-established surrogate for studying human cranial suture biology. In mice, all sutures with the exception of the posterior frontal (PF) suture remain patent throughout life. Histology is regarded as the gold standard for analyzing sutures. On this basis, PF suture fusion begins on day of life 25 and is complete by day 45. Cranial suture histology, however, requires sacrifice of the animal to obtain tissue for analysis. As a result, knowledge of the kinetics of cranial suture fusion is based on a patchwork analysis of many sutures from many different animals. The behavior of a single suture through time is unknown. Our goal is to develop a noninvasive means to repeatedly image mouse cranial sutures in vivo. As a first step, the present study was performed to evaluate microfocal computer tomography (micro-CT) technology for the use of capturing images of a mouse cranium in situ. METHODS: The micro-CT system consists of a microfocal X-ray source and a large format CCD camera optically coupled to a high-resolution X-ray image intensifier, digitally linked to a computer. The PF and sagittal sutures lie in continuity along the midline of the skull. Holes were drilled in the calvaria on both sides of the PF and sagittal sutures of a 45-day-old euthanized mouse. A micro-CT scan of this animal was performed and hundreds of cross-sectional images were generated for the cranium. These images were used to reconstruct three-dimensional volumetric images of the entire cranium. Comparisons were made between (1). the gross specimen and the three dimensional reconstructions; (2). two-dimensional coronal images obtained by micro-CT and those obtained by histology. RESULTS: Analysis of PF and sagittal sutures demonstrated the following: (1). The drilled holes were accurately rendered by micro-CT, when compared to both the gross specimen and the histology. (2). The sagittal suture was found to be patent by both micro-CT and histology. (3). The PF suture is fused by histology, but unexpectedly, the PF suture appears incompletely fused by micro-CT. By micro-CT, however, the anterior and endocranial regions appear more extensively fused than the remainder of the PF suture, a finding consistent with published histologic analysis. CONCLUSIONS: We successfully imaged 45-day-old mouse cranial sutures in situ using micro-CT technology. Precise correlation between histologic sections and radiologic images is difficult, but convincing similarities exist between the gross specimen and images from micro-CT and histology. PF suture fusion in a 45-day-old animal appears different by micro-CT than by histology. One possible explanation for this apparent discrepancy is that suture fusion in histology is determined based on the appearance of bone morphology and not tissue density, as the specimens are necessarily decalcified to section the bone. Micro-CT, on the other hand, distinguishes tissues on the basis of density. Newly forming bone may require bone matrix formation prior to complete calcification; PF suture in 45-day-old mice may be morphologically complete but incompletely ossified. Studies correlating histologic and micro-CT assessment of suture development are underway. Micro-CT appears to be a promising method for noninvasive imaging of mouse cranial suture.