Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.     

Decision-making in pediatric blunt solid organ injury: A deep learning approach to predict massive transfusion,need for operative management,and mortality risk

BackgroundThe principal triggers for intervention in the setting of pediatric blunt solid organ injury (BSOI) are declining hemoglobin values and hemodynamic instability. The clinical management of BSOI is, however, complex. We therefore hypothesized that state-of-art machine learning (computer-based) algorithms could be leveraged to discover new combinations of clinical variables that might herald the need for an escalation in care. We developed algorithms to predict the need for massive transfusion (MT), failure of non-operative management (NOM), mortality, and successful non-operative management without intervention, all within 4 hours of emergency department (ED) presentation.MethodsChildren (≤ 18 years) who sustained a BSOI (liver, spleen, and/or kidney) between 2009 and 2018 were identified in the trauma registry at a pediatric level 1 trauma center. Deep learning models were developed using clinical values [vital signs, shock index-pediatric adjusted (SIPA), organ injured, and blood products received], laboratory results [hemoglobin, base deficit, INR, lactate, thromboelastography (TEG)], and imaging findings [focused assessment with sonography in trauma (FAST) and grade of injury on computed tomography scan] from pre-hospital to ED settings for prediction of MT, failure of NOM, mortality, and successful NOM without intervention. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were used to evaluate each model's performance.ResultsA total of 477 patients were included, of which 5.7% required MT (27/477), 7.2% failed NOM (34/477), 4.4% died (21/477), and 89.1% had successful NOM (425/477). The accuracy of the models in the validation set was as follows: MT (90.5%), failure of NOM (83.8%), mortality (91.9%), and successful NOM without intervention (90.3%). Serial vital signs, the grade of organ injury, hemoglobin, and positive FAST had low correlations with outcomes.ConclusionDeep learning-based models using a combination of clinical, laboratory and radiographic features can predict the need for emergent intervention (MT, angioembolization, or operative management) and mortality with high accuracy and sensitivity using data available in the first 4 hours of admission. Further research is needed to externally validate and determine the feasibility of prospectively applying this framework to improve care and outcomes.Level of EvidenceIIIStudy TypeRetrospective comparative study (Prognosis/Care Management).     

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.     

Toll-like receptor-4 signaling mediates pulmonary neutrophil sequestration in response to gram-positive bacterial enterotoxin

BACKGROUND: Toll-like receptors (TLRs) serve as mediators of innate immune responses to pathogen-associated molecular patterns (PAMPs) which include lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB). TLR-4 is thought to act as the primary effector of LPS recognition and TLR-2 is thought to mediate responses to Gram-positive bacterial proteins. Chemokines such as macrophage inflammatory protein (MIP-2) are peptides that are responsible for lung neutrophil (PMN) sequestration following an infectious or inflammatory insult. Given the Gram-positive origin of SEB, we hypothesized that mice with altered TLR-4 signaling would exhibit no difference in lung PMN sequestration following SEB when compared to wild-type mice. METHODS: Wild-type and TLR-4 mutant mice were administered intratracheal saline, LPS (Escherichia coli 0.1 mg/kg), or SEB (1 mg/kg). After 24 h, lung PMN accumulation was determined by myeloperoxidase (MPO) assay and bronchoalveolar lavage fluid cell count (BALfcc). Total lung and BALf MIP-2 was measured by enzyme-linked immunosorbent assay. RESULTS: There was an increase in lung PMN accumulation (by both MPO and BALfcc) and MIP-2 following LPS and SEB in wild-type mice compared to saline-treated controls. In contrast, TLR-4 mice failed to exhibit an increase in lung MIP-2 or PMN accumulation following either LPS or SEB compared to wild-type mice. CONCLUSIONS: TLR-4 mutant mice are unresponsive to intratracheal LPS. SEB elicited an increase in lung MIP-2 and PMN accumulation in wild-type mice. However, TLR-4 mutant mice were protected from this process. This suggests that TLR-4 signaling may mediate the responses to other PAMPs in addition to LPS.     

Electromyographic investigation of unstable patella before and after its realignment operation

Background:

Patellar dislocations are either due to superolateral contracture of the soft tissue or imbalance of the power between the vastus medialis (VM) and the vastus lateralis (VL). The imbalance of muscle power as an etiology of patellar dislocation has not been studied. Hence, we studied the recurrent, habitual and permanent dislocations of the patella with an electromyogram (EMG) of the vastus medialis, vastus lateralis, and pes anserinus, before and after realignment operations, to document the muscle imbalance and effectiveness of the realignment operation.

Materials and Methods:

An electromyographic investigation was carried out on the vastus medialis and vastus lateralis in nine recurrent, 20 habitual, and 13 permanent dislocations of the patella, before and after their realignment operations. Pes anserinus transposition, which acted as a medial stabilizer of the patella, was also investigated with an EMG study, to understand its role on patellar stability at 0°, 30°, 60°, 90°, 120°, 150°, and full flexion of the knee. The age of the patients varied from nine to 30 (mean 15) years. There were 24 males and 18 females. Twenty-six patellar dislocations were on the right and 16 were on the left side.

Results:

Electromyographic pictures reveal subnormal activity of the vastus medialis in all types of dislocations and similar activities of the vastus lateralis in permanent and habitual dislocations recorded pre operatively, which recovered to almost normal values postoperatively, at the mean one-year follow-up. Pes anserinus, which was used for medial stabilization of the patella after its realignment, maintained normal EMG activity before and after the operation.

Conclusion:

This study is significant for understanding the imbalance of muscle activities in patients with an unstable patella, which can be rectified without recurrence after pes anserinus transposition.     

TNF receptor I mediates chemokine production and neutrophil accumulation in the lung following systemic lipopolysaccharide.

BACKGROUND: Tumor necrosis factor (TNF)-alpha is a critical effector of lipopolysaccharide (LPS)-induced acute lung injury, and its effects are mediated by two structurally related receptors, RI and RII. Cellular adhesion molecules and C-X-C chemokines (Keratinocyte chemoattractant (KC) and macrophage inflammatory protein [MIP]-2) regulate tissue neutrophil polymorphonuclear neutrophil (PMN) accumulation in a multitude of inflammatory states. We hypothesized that TNFRI signaling dictates PMN accumulation in the lung via regulation of chemokine molecule production. Therefore, the purposes of this study were to (1) delineate LPS-induced lung TNF-alpha production and (2) characterize the contribution of both TNF receptors to lung chemokine production and neutrophil influx following systemic LPS. METHODS: Wild-type or TNFRI and TNFRII knockout (KO) mice were injected with vehicle (saline) or LPS (Escherichia coli 0.5 mg/kg intraperitoneally). After 2, 4, 6, or 24 h, lungs were analyzed for TNF-alpha and chemokine (KC and MIP-2) protein expression (enzyme-linked immunosorbent assay) and PMN accumulation (myeloperoxidase assay). RESULTS: There was an increase in total lung TNF-alpha (vehicle, 5.0 +/- 1.2 pg/mg total protein vs LPS, 950 +/- 318; P < 0.05) after LPS. Lung chemokine production and PMN accumulation were also increased compared to vehicle-injected mice. Lung chemokine production and PMN accumulation were significantly lower in TNFRI KO, but not TNFRII KO, mice, despite no difference in TNF-alpha production (TNFRI KO, 925 +/- 301 vs TNFRII KO, 837 +/- 267, P = 0.82). CONCLUSIONS: Acute lung injury following systemic LPS administration is characterized by increased lung (1) TNF-alpha production, (2) C-X-C chemokine production, and (3) neutrophil accumulation. The maximal effect of LPS-induced lung neutrophil accumulation appears to be dependent upon the TNFRI receptor but not the TNFRII receptor. .     

The injured child is resistant to multiple organ failure: a different inflammatory response?

BACKGROUND: Although postinjury multiple organ failure (MOF) is a well-described phenomenon in adults, the incidence of this syndrome in children is unknown. The purpose of this study was to describe the incidence, course, and severity of pediatric postinjury MOF. We hypothesized that the incidence and severity of postinjury MOF in children would be less when compared with adults. METHODS: Patients were retrospectively identified from the trauma registry of a regional pediatric trauma center and an adult Level I trauma center with pediatric commitment for a 3-year period. All trauma patients less than 16 years old who survived for longer than 24 hours and had an Injury Severity Score > 15 were eligible. An accepted MOF score was used. Categorical variables were compared by chi2 and continuous variables by t test. A value of p< 0.05 was considered statistically significant. RESULTS: Of 534 patients identified, 334 (63%) were admitted for evaluation of isolated head injury and excluded from further analysis. The rate of postinjury MOF in children was found to be only 3%, with a low (17%) mortality when compared with historical adult data (50%). CONCLUSION: The incidence of postinjury MOF in the child is less than in the adult, given equivalent injury severity. These observations solidify the contention that postinjury MOF is rare in children, and is less severe when it occurs. Delineating the mechanism(s) whereby children are protected from postinjury MOF may provide insight into the development of strategies to prevent MOF in other age groups as well as various disease states.