Detection and localisation of hip fractures on anteroposterior radiographs with artificial intelligence: proof of concept.

AIM: To investigate the feasibility of applying a deep convolutional neural network (CNN) for detection/localisation of acute proximal femoral fractures (APFFs) on hip radiographs. MATERIALS AND METHODS: This study had institutional review board approval. Radiographs of 307 patients with APFFs and 310 normal patients were identified. A split ratio of 3/1/1 was used to create training, validation, and test datasets. To test the validity of the proposed model, a 20-fold cross-validation was performed. The anonymised images from the test cohort were shown to two groups of radiologists: musculoskeletal radiologists and diagnostic radiology residents. Each reader was asked to assess if there was a fracture and localise it if one was detected. The area under the receiver operator characteristics curve (AUC), sensitivity, and specificity were calculated for the CNN and readers. RESULTS: The mean AUC was 0.9944 with a standard deviation of 0.0036. Mean sensitivity and specificity for fracture detection was 97.1% (81.5/84) and 96.7% (118/122), respectively. There was good concordance with saliency maps for lesion identification, but sensitivity was lower for characterising location (subcapital/transcervical, 84.1%; basicervical/intertrochanteric, 77%; subtrochanteric, 20%). Musculoskeletal radiologists showed a sensitivity and specificity for fracture detection of 100% and 100% respectively, while residents showed 100% and 96.8%, respectively. For fracture localisation, the performance decreased slightly for human readers. CONCLUSION: The proposed CNN algorithm showed high accuracy for detection of APFFs, but the performance was lower for fracture localisation. Overall performance of the CNN was lower than that of radiologists, especially in localizing fracture location.

Efficacy and Safety of Transnasal CoolStat Cooling Device to Induce and Maintain Hypothermia.

Targeted temperature management (TTM) is recommended as a standard of care for postcardiac arrest patients. Current TTM methods have significant limitations to be used in an ambulatory setting. We investigated the efficacy and safety of a novel noninvasive transnasal evaporative cooling device (CoolStat™). Eleven Yorkshire pigs underwent hypothermia therapy using the CoolStat device. CoolStat induces evaporative cooling by blowing dehumidified ambient air over the nasal turbinates in a unidirectional fashion. CoolStat's efficacy and safety were assessed by applying different cooling strategies (groups A, B and C). In group A (efficacy study; n = 5, TTM for 8 hours), time to achieve brain target temperature (2°C reduction from baseline), and the percentage of time in which the temperature ranged within ±0.5°C after reaching the target temperature were investigated. In the safety assessment (groups B and C), two worst-case therapy situations were reproduced: in group B (n = 3), continuous maximum air flow (65 L/min) was applied without temperature control and, in group C (n = 3), subjects underwent 24-hour TTM (prolonged therapy). Hemodynamic and respiratory parameters, nasal mucosa integrity (endoscopic assessment), and other therapy-related adverse effects were evaluated. Efficacy study: CoolStat cooling therapy successfully induced and sustained managed hypothermia in all subjects. Brain target temperature was achieved in 0.5 ± 0.6 hours and kept within a ±0.5°C range for the therapy duration (99.9% ± 0.1%). All animals completed the safety studies. Maximum air flow (group B) and 24-hour (group C) therapies were well tolerated and no significant damage was observed on nasal mucosa for neither of the groups. CoolStat was able to efficiently induce and maintain hypothermia using unidirectional high flow of dry air into the nostrils of porcine models. CoolStat therapy was well tolerated and no damage to nasal mucosa was observed under either maximum air flow or prolonged therapy.

Knee contact forces and lower extremity support moments during running in young individuals post-partial meniscectomy.

PURPOSE: While partial meniscectomy results in a compromised tibiofemoral joint, little is known regarding tibiofemoral joint loading during running in individuals who are post-partial meniscectomy. It was hypothesized that individuals post-partial meniscectomy would run with a greater hip support moment, yielding reduced peak knee extension moments and reduced tibiofemoral joint contact forces. METHODS: 3-D Treadmill running mechanics were evaluated in 23 athletic individuals post-partial meniscectomy (37.5 ± 19.0 months post-partial meniscectomy) and 23 matched controls. Bilateral hip, knee and ankle contributions to the total support moment and the peak knee extension moment were calculated. A musculoskeletal model estimated peak and impulse tibiofemoral joint contact forces. Knee function was quantified with the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: During running, the partial meniscectomy group had a greater hip support moment (p = 0.002) and a reduced knee support moment (p < 0.001) relative to the total support moment. This movement pattern was associated with a 14.5 % reduction (p = 0.019) in the peak knee extension moment. Despite these differences, there were no significant group differences in peak or impulse tibiofemoral joint contact forces. Lower KOOS Quality of Life scores were associated with greater hip support moment (p = 0.004, r = -0.58), reduced knee support moment (p = 0.006, r = 0.55) and reduced peak knee extension moment (p = 0.01, r = 0.52). CONCLUSIONS: Disordered running mechanics are present long term post-partial meniscectomy. A coordination strategy that shifts a proportion of the total support moment away from the knee to the hip reduces the peak knee extension moment, but does not equate to reduced tibiofemoral joint contact forces during running in individuals post-partial meniscectomy. LEVEL OF EVIDENCE: III.

Comparison of Bio-Rad %CDT TIA and CDTect as laboratory markers of heavy alcohol use and their relationships with gamma-glutamyltransferase.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) is used as a serum marker for heavy drinking. We compared a new Bio-Rad %CDT TIA assay with the CDTect assay; we also compared both to gamma-glutamyltransferase (GGT) as markers of heavy drinking. METHODS: Serum samples of well-defined alcoholics (n = 404) and matched (age, race, and gender) social drinkers (204) from 10 clinical centers were assayed with both CDT assays. Both assays use microcolumn separation after iron saturation, followed by enzyme immunoassay (CDTect) or turbidimetric immunoassay (Bio-Rad %CDT). In the latter, CDT is expressed as a percentage of total transferrin. RESULTS: The slope and intercept [95% confidence intervals (CIs)] for linear regression of results obtained by the %CDT-TIA (as percentage) and CDTect (units/L) assays were 0.091 (0.088-0.097) and 0.70% (0.54-0.86%), respectively (S(y/x) =1.30%; r = 0.848). The areas under the ROC curves (95% CIs) for CDTect and Bio-Rad %CDT TIA were 0.89 (0.86-0.92) and 0.88 (0.85-0.91), respectively, for men (P, not significant) and 0.76 (0.72-0.80) and 0.72 (0.68-0.76) for women (P, not significant). When CDT (CDTect or Bio-Rad %CDT) was combined with GGT (either one positive), the clinical sensitivity in men was 90% for both assays, and specificities were 81% and 84%, respectively; sensitivities in women were 75% and 76%, respectively, and specificities were 87% and 91%. CONCLUSION: The new Bio-Rad %CDT TIA assay compares favorably to the widely studied CDTect assay in the detection of alcohol-use disorders.

The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney.

Synthesis of Tyr in the human body occurs by hydroxylation of the indispensable amino acid Phe. Until now, it was believed that in humans, this process was restricted to the liver, but we provide compelling evidence of production of Tyr from Phe in the kidney. To determine whether the human kidney produces Tyr, we measured Tyr balance, the Tyr appearance rate, and the Phe-to-Tyr conversion in 12 healthy human subjects by using [(15)N]Phe and [(2)H(4)]Tyr as tracers. Renal plasma flow was measured by using paraaminohippurate, and sampling from the femoral artery and renal veins was performed. The results were compared with those obtained in 12 control subjects undergoing hepatic vein catheterization and infusion of identical tracers. In all 12 subjects, there was a net uptake of Phe by the kidney (2.2 +/- 1.2 micromol/min), whereas Tyr was released (5.3 +/- 1.5 micromol/min). In contrast, there was a net uptake of both Phe (9.5 +/- 1.2 micromol/min) and Tyr (14.3 +/- 1.3 micromol/min) by the splanchnic bed. Phe conversion to Tyr occurred at a rate of 5.2 +/- 1.2 micromol/min in kidney and 3.0 +/- 0.7 micromol/min in the splanchnic bed. The kidney contributed a substantial amount of Tyr to the systemic circulation where the splanchnic bed was a net remover of Tyr. Our results demonstrate that the kidney is the major donor of Tyr to the systemic circulation by its conversion of Phe to Tyr. This observation may have important clinical implications for patients with both renal and hepatic disease, who may be at risk of Phe overloading and Tyr deficiency, and it should be considered when parenteral or enteral nutrients are administered rich in Phe and low in Tyr.

Calcium oxalate crystal attachment to cultured kidney epithelial cell lines.

PURPOSE: Cultured kidney epithelial cell lines have frequently been used in urolithiasis research, and in particular in studies related to the interactions between stone crystals and cell membranes. There is evidence that when epithelial cell lines are transformed or serially passed to immortalize them, they experience changes in both cell physiology and morphology. Stone research utilizing cell cultures is frequently necessary due to the lack of an animal model for spontaneous stone disease. However, the interpretation of these cell culture research studies might be clouded by any significant differences in cell physiology between primary cells and continuous cell cultures. Therefore, the present study was conducted to compare calcium oxalate monohydrate (COM) crystal attachment to two primary kidney epithelial cell lines and to various continuous cell lines. MATERIALS AND METHODS: The cell lines surveyed were primary mouse proximal tubule cells (pMPT), primary inner medullary collecting duct cells (pIMCD), semi-continuous inner medullary collecting duct cells (cIMCD), BSC-1 cells, COS-1 cells, LLC-PK1 cells, MDCK cells, NRK-52E cells, and OK cells. All cell lines were cultured under identical conditions and the amount of COM attachment was measured using radioactive labeled COM crystals. RESULTS: COM crystal interaction with continuous kidney epithelial cells varied by a factor of two among the different cell lines. In general, cells that grew as regular, confluent cell monolayers, such as pMPT, pIMCD and cIMCD cells, exhibited the lowest levels of crystal attachment. Neither changes in membrane fluidity nor loss of normal epithelial cell membrane asymmetry seemed to correlate well with crystal attachment. After nine days of continuous cell culture, COM attachment to cIMCD cells dropped by 61 percent while crystal attachment to MDCK cells remained unchanged. It is unclear what makes these cell lines more resistant to crystal attachment compared to continuous cell lines. CONCLUSIONS: The significant difference in COM attachment between primary kidney epithelial cells and continuous epithelial cell cultures and the apparent differences in growth morphology between primary and continuous cell cultures must be considered when selecting a cell line for use in kidney stone research. Comparison of cIMCD cells and MDCK cells during extended culture time revealed one possible explanation for the differences in COM attachment: the formation of a mature, end-differentiated, non-dividing cell monolayer could protect the cells from crystal attachment.

The dependence on membrane fluidity of calcium oxalate crystal attachment to IMCD membranes.

The development of urolithiasis is a multifaceted process, starting with urine supersaturation and ending with the formation of mature renal calculi. The retention of microcrystals by kidney tubule epithelium cell membranes has been proposed as a critical event in the process. To date, attachment of kidney stone constituent crystals to urothelial cells has been demonstrated both in vitro and in vivo yet the mechanism of crystal attachment remains unknown. We hypothesize that for effective stone crystal attachment to the epithelium there must be cell membrane rearrangement that would allow for long-range bonding between the stone crystal and the cell membrane. This rearrangement may be influenced by the physical state of the membrane. The current study examines calcium oxalate monohydrate (COM) crystal attachment to inner medullary collecting duct (IMCD) cells following changes in cell membrane fluidity. Radioactively labeled COM crystals were used to quantitate crystal attachment. Membrane fluidity was altered by changing temperature, cell membrane cholesterol content, or extended length of cell culture. Crystal attachment to IMCD cells was directly correlated to changes in membrane fluidity. This finding was consistently observed regardless of the method used to alter membrane fluidity. The results are consistent with the theory that the ability to form a crystal attachment region on the cell surface may be related to the ease of rearrangement of membrane components at the cell surface. Variations in the urothelial cell environment during certain pathological conditions in the kidney could induce these physical perturbations and prime kidney epithelial cells at or near the papillary tip to bind COM crystals.

Surface exposure of phosphatidylserine increases calcium oxalate crystal attachment to IMCD cells.

The development of urolithiasis is a multifaceted process, starting at urine supersaturation and ending with the formation of mature renal calculi. The retention of microcrystals by the urothelial cell membrane is a critical event in the process. The current study examines calcium oxalate monohydrate (COM) crystal attachment to inner medullary collecting duct (IMCD) cells following selective changes in cell membrane phospholipid composition. Both primary culture of IMCD cells and a continuous IMCD cell line were used for these studies. Cell membrane composition was selectively altered by either exogenous addition of membrane phospholipids or using membrane lipid scrambling agents. Enrichment with anionic phospholipids was found to greatly increase attachment of crystals to the cells. This increased attachment correlated with the exposure of phosphatidylserine (PS) on the exofacial leaflet of the cell membrane as demonstrated by the use of the membrane scrambling agent A-23187. Furthermore, the increased COM attachment following PS exposure could be blocked by incubating the cells with the PS-specific binding protein, annexin V. These results support the hypothesis that exposure of PS head groups on the papillary epithelial cell surface may mediate stone crystal attachment to the kidney tubule cell epithelium in the renal papilla, possibly as an initiating event in urolithiasis.

Calcium oxalate-crystal membrane interactions: dependence on membrane lipid composition.

PURPOSE: Urolithiasis is clearly a multifaceted process, progressing from urine supersaturation to the formation of mature renal calculi. Retention of microcrystals by the urothelium is a critical event in stone maturation. Membrane phospholipids appear to be involved in the attachment of stone crystals to kidney epithelium. MATERIALS AND METHODS: The current study quantitates crystal-membrane interactions following selective changes in the red blood cell (RBC) membrane phospholipid composition by using a crystal-induced membranolytic assay. RESULTS: Membrane enrichment with anionic phospholipids was found to greatly increase crystal-membrane interactions. Crystal-membrane interaction was associated with an increase in the negative charge on the RBC membrane surface. CONCLUSIONS: Specific membrane compositions seem to facilitate the formation of crystal attachment region on the RBC surface that is necessary for effective crystal attachment to the cell membrane.

Highly efficient protein separations in high-performance capillary electrophoresis, using hydrophilic coatings on polysiloxane-bonded columns.

Three methods for preparing hydrophilic coatings on polysiloxane bonded CElect H-type capillary electrophoresis columns have been shown. The polyalkylsiloxane-bonded phase is the first coating layer on the capillary surface, and nonionic surfactant, hydrophilic polymer, or polymer surfactant, adsorbed onto this first later through hydrophobic interactions, forms the second coating layer. The resultant capillary surfaces are inert, hydrophilic, and suitable for highly efficient protein separations. The effectiveness and applicability of these capillary surface modification methods were tested for the separations of a variety of proteins over a wide range of buffer pH values under different capillary electrophoretic operations modes.

A multivariate analysis of determinants of survival for patients with squamous cell carcinoma of the head and neck.

The prognosis for patients with squamous cell carcinoma of the head and neck remains poor, despite refinements in conventional therapy and experimental protocols using alternative treatment modalities. Clinical characteristics reported to influence survival have included age and sex of the patient, the therapy used, location of the primary tumor, and stage at initial presentation. However, such variables are highly correlated, and previous reports have lacked sufficient statistical analysis to assess the independent influence of these competing variables on survival. To better define the principal determinants of survival, we used a Cox multivariate regression analysis of 542 patients with invasive squamous cell carcinoma of the head and neck treated exclusively at our institution from 1962 to 1976. All patients were followed for a minimum of 5 years after diagnosis, with 98% complete follow-up achieved. Stage at initial presentation was the single-most important factor influencing survival for all tumor locations (p less than 0.0001). Advanced age (p = 0.001) and location of the primary tumor in the tonsillar area (p = 0.01) were also independently associated with an inferior survival. The type of therapy used and sex of the patient did not significantly influence survival after controlling for stage. These data emphasize the need for early diagnosis and treatment of squamous cell carcinoma of the head and neck and underscore the limitations of current therapeutic approaches. Future investigations should incorporate multivariate statistical techniques whenever possible, and additional efforts must be directed at basic research into the biology and immunologic characteristics of these tumors in an attempt to identify innovative therapeutic modalities.

Burn-induced cosmetic disfigurement: can it be measured reliably?

Cosmetic disfigurement was measured reliably by averaging the ratings of four or more viewers of color slide photographs of severely burned children and young adults. Raters were clinical and nonclinical staff at a burn hospital. Reliability for four-person rating of overall cosmetic disfigurement (unclothed) was .94; for overall disfigurement (clothed) it was .86; for irregularity, thickness, and discoloration it was .78, .79, and .72, respectively. Profession, sex, and years of contact with burned patients did not influence inter-rater agreement. Any randomly selected panel of four raters produced reliable average ratings. The effect of impaired skin texture on overall ratings of cosmetic disfigurement (both clothed and unclothed) was three to five times as important as the effect of impaired color. Despite its subjectivity, cosmetic disfigurement can be measured reliably. This report describes a formal procedure for such measurement and discusses ways of using that procedure to improve patient care.

Squamous cell carcinoma of the head and neck at the Massachusetts General Hospital: a comparison of biologic characteristics in men and women.

Little is known about the biologic behavior of squamous cell carcinoma of the head and neck in women. A few recent reports for selected sites have suggested that these tumors may be becoming more common in women. To evaluate potential differences between males and females with squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx and to assess whether the proportion of females with this disease is increasing, the authors have undertaken a retrospective review of 542 consecutive patients treated at our institution from 1962 through 1976. We report here the first detailed comparison of males and females with squamous cell carcinoma of the head and neck, with attention directed to stage at initial presentation, choice of therapy, response to therapy, age distribution, survival, and prevalence of second primary malignancies. It has been widely published that survival for women with squamous cell carcinoma of the head and neck is superior to that for men, and this has been attributed to a difference in the biologic characteristics of the disease between the two sexes. Although overall survival calculations in our series suggested a significantly better survival rate for women than for men, these rates were strongly influenced by the larger proportion of women (64%) who had stage I or II disease, compared with only 50% of men. When survival was compared stage by stage, there was no significant difference in survival between the two sexes. The proportion of females in the combined study population was 35%, increasing from 33% in the first 5 years of the study period to 40% in the last 5 years. Among patients born before 1920, 34% were female compared with 43% of patients born after 1920. Of the 13 patients less than 40 years of age at diagnosis, 62% were female. The rising proportion of women during the 15-year study period, particularly among young patients and those in more recent birth cohorts, strongly suggests that squamous cell carcinoma of the head and neck is increasing among women in this referral population. A review of the literature indicates that this trend began more than 40 years ago.

Clinical behavior and results of current therapeutic modalities for squamous cell carcinoma of the buccal mucosa.

A retrospective analysis of 28 patients who received therapy for squamous cell carcinoma of the buccal mucosa at the Massachusetts General Hospital from January 1962 through December 1976 is presented. The patients ranged in age from 42 to 78 years; the majority of patients presented with disease at 50 years or more. The proportion of females in this series (43 per cent) represented a dramatic increase compared with previous reports from other large centers. The 29 per cent rate of metachronous or synchronous second primary malignant disease is increased significantly over that expected for the general population. Uncontrolled disease above the clavicle continues to be the major site of therapeutic failure. The development of co-operative multicenter randomized prospective protocols to evaluate the efficacy of various combinations of current therapy methods in order to improve patient survival from this devastating disease are encouraged.

Squamous cell carcinoma of the alveolar ridge and palate. A 15-year survey.

A retrospective review of 82 patients treated at the Massachusetts General Hospital from 1962 through 1976 for squamous cell carcinoma of the maxillary and mandibular alveolar ridge and soft and hard palates is presented. Stage at first presentation, clinical features of the disease, analysis of current therapeutic modalities, survival statistics, and prevalence of second primary malignancies are analyzed and compared with reports from other large centers.

Squamous cell carcinoma of the tongue: a comparison of the anterior two thirds of the tongue with its base.

A retrospective analysis of 176 patients with squamous cell carcinoma of the tongue has been reported. The tongue base and mobile tongue, believed to behave as two clinically distinct anatomic areas, have been compared and contrasted. Women comprised 25 percent of the patients with tumors of the base of the tongue and 45 percent of those with mobile tongue lesions, an increase over previous reports for both locations. The majority of patients with squamous cell carcinoma of the tongue base (77 percent) presented with advanced (stage III or IV) lesions at time of initial clinical and diagnostic staging, compared with only 33 percent of those with cancer of the mobile tongue. There was no significant difference in survival between the two locations when survival rates were compared stage by stage. The decreased overall survival frequently reported for patients with squamous cell carcinoma of the tongue base compared with the survival for patients with tumors of the mobile tongue may be due to the disproportionately high number of patients with cancer of the tongue base who present with advanced disease. Survival rates have not significantly improved when compared with other retrospective series reported in the past 40 years. We strongly urge the development of intercenter, multidisciplinary, cooperative, prospective, protocols to assess combinations of currently accepted therapeutic modalities in the hope of improving treatment of this devastating disease.