The origin of fatal pulmonary emboli: a postmortem analysis of 500 deaths from pulmonary embolism in trauma,surgical, and medical patients

Background

The traditional theory that pulmonary emboli (PE) originate from the lower extremity has been challenged.

Methods

All autopsies performed in Los Angeles County between 2002 and 2010 where PE was the cause of death were reviewed.

Results

Of the 491 PE deaths identified, 36% were surgical and 64% medical. Venous dissection for clots was performed in 380 patients; the PE source was the lower extremity (70.8%), pelvic veins (4.2 %), and upper extremity (1.1%). No source was identified in 22.6% of patients. Body mass index (adjusted odds ratio [AOR] 1.044, 95% confidence interval [CI] 1.011 to 1.078, P = .009) and age (AOR 1.018, 95% CI 1.001 to 1.036, P = .042) were independent predictors for identifying a PE source. Chronic obstructive pulmonary disease (AOR .173, 95% CI .046 to .646, P = .009) was predictive of not identifying a PE source.

Conclusions

Most medical and surgical patients with fatal PE had a lower extremity source found, but a significant number had no source identified. Age and body mass index were positively associated with PE source identification. However, a diagnosis of chronic obstructive pulmonary disease was associated with no PE source identification.     

Evaluation of the Antimicrobial Protection of Pharmaceutical Kaolin and Talc Modified with Copper and Zinc

Six pharmaceutical pastes were prepared using chemically modified kaolin and talc powders. Tests were conducted to determine their structural and chemical characteristics as well as their antimicrobial protection, thus rendering them suitable for cosmetic and pharmaceutical uses. Kaolin and talc were treated chemically via the cation exchange method to load the clay particles with copper and zinc ions, two cations well known for their antimicrobial properties. Mineralogical analyses were conducted by using X-ray diffraction (XRD) before and after the modification, confirming the mineralogical purity of the samples. Scanning electron microscopy was also used in conjunction with energy dispersed spectroscopy (SEM-EDS) to obtain chemical mapping images, revealing the dispersion of the added metals upon the clay minerals surfaces. Moreover, chemical analysis has been performed (XRF) to validate the enrichment of the clays with each metal utilizing the cation exchange capacity. All modified samples showed the expected elevated concentration in copper or zinc in comparison to their unmodified versions. From the X-ray photoelectron spectroscopy (XPS), the chemical state of the samples’ surfaces was investigated, revealing the presence of salt compounds and indicating the oxidation state of adsorbed metals. Finally, the resistance of pastes in microbial growth when challenged with bacteria, molds, and yeasts was assessed. The evaluation is based on the European Pharmacopeia (EP) criteria.     

Proinflammatory effects of TH2 cytokines in a murine model of chronic small intestinal inflammation

BACKGROUND & AIMS: Strict T H 1 polarization is believed to underlie the pathogenesis of intestinal inflammation in Crohn's disease. In the present study we tested the hypothesis that TH2 cytokines also may participate in disease development in SAMP1/YitFc mice that spontaneously develop terminal ileitis with perianal manifestations. METHODS: Cytokine messenger RNA (mRNA) expression was studied by real-time polymerase chain reaction (PCR). Lamina propria mononuclear cells (LPMCs) were purified and stimulated cytokine secretion was analyzed. Blockade of interferon (IFN)-gamma or interleukin (IL)-4 was performed by using specific neutralizing monoclonal antibodies (MAbs). CD4+/IL-4-secreting lymphocytes were purified from SAMP1/YitFc mesenteric lymph nodes (MLNs) and their ability to induce ileitis was tested after transfer to SCID recipients. RESULTS: Initiation of ileitis in SAMP1/YitFc mice was T H 1-mediated because up-regulation of IFN-gamma and tumor necrosis factor (TNF) preceded the histologic injury, whereas IFN-gamma neutralization prevented the development of chronic inflammation (P <.005) by interfering with the expansion of lymphocytes. In contrast, the establishment of chronic ileitis coincided with significant increases in IL-5 (35x) and IL-13 (29x) mRNA expression (P <.005), as well as in T H 2 cytokine secretion by lamina propria lymphocytes (P <.05 vs. AKR controls). IL-4 blockade diminished IFN-gamma mRNA expression and significantly ameliorated the severity of established ileitis (P <.05) by decreasing the histologic indices for villous distortion and active inflammation. In addition, IL-4 augmented the in vitro IFN-gamma secretion by lymphocytes, whereas IL-4-secreting CD4+ lymphocytes were sufficient for adoptively transferring ileitis to SCID recipients. CONCLUSIONS: Our results indicate that both TH1 and TH2 pathways mediate Crohn's-like ileitis and suggest that combined TH1/TH2 manipulation may offer a therapeutic advantage for the treatment of Crohn's disease.     

Regional Nodal Metastatic Disease Is the Strongest Predictor of Survival in Patients with Thin Vertical Growth Phase Melanomas: A Case for SLN Staging Biopsy in These Patients

BACKGROUND: The benefit of sentinel lymph node (SLN) biopsy for patients with thin (< or =1.0 mm) melanomas, even for prognostic value, is controversial. This may partly result from the relatively small number and short follow-up of SLN-positive patients in this group. Previously, we have shown that clinical regional nodal metastatic disease (RNMD) serves as a good surrogate for SLN positivity. Here, we use RNMD as a validated surrogate for SLN positivity and examine its prognostic value in a large pre-SLN group of patients with thin vertical growth phase (VGP) lesions who would today commonly be offered SLN biopsy in our practice. METHODS: Between 1972 and 1991, 472 patients with thin VGP melanomas with at least 10 years' follow-up were eligible for the study. Kaplan-Meier survival curves were computed for patients with and without RNMD. A multivariate Cox model and classification tree analysis were used to evaluate clinical and histopathologic predictors of survival. RESULTS: Sixty-seven patients (14.2%) developed recurrence, 53.7% of whom developed RNMD. Forty-five patients (9.5%) experienced melanoma-related deaths (MRD). The most statistically significant predictor of MRD was RNMD (hazard ratio [HR] 13.5, P < .0001). Thickness (HR 10.5, P = .004), axial location (HR 4.6, P = .001), and age >60 years (HR 2.7, P = .005) additionally were independently associated with an increased risk of MRD. RNMD patients demonstrated a 44.4% 10-year disease-specific mortality. CONCLUSIONS: RNMD was the most statistically significant factor associated with MRD in patients with thin VGP lesions. This supports the prognostic use of SLN biopsy in this group, recognizing that additional factors, including thickness, axial location, and older age were independently associated with a worse survival outcome.     

Hypercoagulable state due to alcohol-paracetamol syndrome producing acute limb ischemia

The authors describe a man with alcohol-paracetamol syndrome and hepatic failure who presented with acute arterial thrombosis of the left limb. The patient has jaundice, increased serum transaminase levels, and significant coagulopathy, with elevated international normalized ratio and prolonged prothrombin time. A transient hypercoagulable state due to liver failure is documented, characterized by acquired deficiencies of antithrombin III, protein C, and protein S. Laboratory and molecular testing for inherited hypercoagulable disorders during the follow-up period is positive for increased levels of factor VIII. The patient undergoes successful thrombectomy and receives intensive symptomatic and causal treatment, resulting in complete recovery. The patient is discharged 20 days after admission on a regimen of acenocoumarol.     

Rituximab-induced nonspecific interstitial pneumonia like reaction in a patient with idiopathic thrombocytopenic purpura

Rituximab, a chimeric anti-CD20 IgG1 monoclonal antibody, is an effective treatment for haematological autoimmune diseases such as idiopathic thrombocytopenic purpura (ITP). A 72-year-old man was diagnosed with idiopathic thrombocytopenic purpura (ITP). After receiving 4 cycles of rituximab in one month complete response was achieved. However, three weeks after the last infusion he presented to the haematology department with fever, productive cough and dyspnea and severe hypoxemia. HRCT of the thorax revealed patchy areas of ground glass opacities throughout both lungs and small peripheral consolidations were seen. Transbronchial biopsy showed interstitial thickening and type II pneumocyte activation with interstitial pneumonia. Bronchoalveolar lavage showed increased eosinophils. The patient was treated with three pulses of 1 gr iv methylprednisolone and then gradually switched to 15 mg of prednisolone for 3 months. The dyspnea and tachypnea gradually improved, in addition to blood oxygenation and a follow up HRCT 3 months later showed a significant resolution of lesions.Severe lung toxicity like acute respiratory distress syndrome, cryptogenic organizing pneumonia, pneumonitis, and interstitial lung disease are very rare, with most of the knowledge coming from case reports. Rituximab-induced interstitial lung disease (R-ILD) is a rare complication. To the best of our knowledge, 23 cases of R-ILD have been reported in the literature; 22 of them were treated with R-CHOP for NHL and only one was receiving rituximab for ITP. We report the second case to develop this complication for a non-malignant disorder.     

Serum transferrin receptors: Distribution and diagnostic performance in pre-school children

Soluble transferrin receptors have gained interest in the field of diagnosing anemias. Reference ranges differ according to the method used for the quantification of sTfR. We aim to explore the distributional properties and diagnostic performance of sTfR in pre-school healthy children as well as in children with β-thalassemia carriers, iron deficiency with normal hematological phenotype (ID) and iron deficiency anemia (IDA). Circulating sTfR as well as biochemical and hematological indices were determined in 521 pre-school children and four groups (normal children, β-thalassemia traits, ID and IDA) were formed. Diagnostic performance and distribution of sTfR according to age and in relation to several parameters were evaluated in every group. Three hundred eighty one children (261 normal, 60 β-thalassemia traits, 44 ID and 16 IDA) aged 1–6 years were included. We found that distribution of sTfR differed significantly among the four groups (Kruskal Wallis p < 0.001) with children in the normal group exhibiting lower concentrations compared to all other. A negative correlation between sTfR and age occurred in the normal (β = − 0.12, p < 0.001) and the ID groups (β = − 0.13, p = 0.035). In the β-thal and IDA groups sTfR is correlated to HbA₂ (β = 0.34, p = 0.001) and ferritin (Spearman's rho = − 0.6, p = 0.014) respectively. An area under the curve equal to 0.63 was achieved by sTfR in distinguishing between normal and ID children. Sensitivity and specificity were 70.5% and 50% respectively at a cut-off of 2.5 mg/l. Levels of sTfR are negatively correlated to age in pre-school children while dyserythropoietic procedures like β-thal, ID, and IDA significantly affect them. These findings indicated that the accuracy of sTfR in diagnosing ID from normal children is limited. Standardization will allow the use of formulas that combine sTfR and ferritin which are of greater diagnostic value than sTfR alone.