In Search of Patient Zero: Visual Analytics of Pathogen Transmission Pathways in Hospitals.

Pathogen outbreaks (i.e., outbreaks of bacteria and viruses) in hospitals can cause high mortality rates and increase costs for hospitals significantly. An outbreak is generally noticed when the number of infected patients rises above an endemic level or the usual prevalence of a pathogen in a defined population. Reconstructing transmission pathways back to the source of an outbreak - the patient zero or index patient - requires the analysis of microbiological data and patient contacts. This is often manually completed by infection control experts. We present a novel visual analytics approach to support the analysis of transmission pathways, patient contacts, the progression of the outbreak, and patient timelines during hospitalization. Infection control experts applied our solution to a real outbreak of Klebsiella pneumoniae in a large German hospital. Using our system, our experts were able to scale the analysis of transmission pathways to longer time intervals (i.e., several years of data instead of days) and across a larger number of wards. Also, the system is able to reduce the analysis time from days to hours. In our final study, feedback from twenty-five experts from seven German hospitals provides evidence that our solution brings significant benefits for analyzing outbreaks.

Comparing complications of small-bore chest tubes to large-bore chest tubes in the setting of delayed hemothorax: a retrospective multicenter cohort study.

BACKGROUND: Previous studies have provided initial data suggesting that small-bore (SB, ≤ 14Fr) chest tubes have the same efficacy as large-bore (LB, > 14 Fr) chest tubes for acute hemothorax (HTX), but data continue to be lacking in the setting of delayed HTX. This study compared complications of SB chest tubes to LB tubes in patients with delayed HTX. METHODS: This was a retrospective observational study across 7.5 yrs. at 6 Level 1 trauma centers. Patients were included if 1) diagnosed with a HTX or > 1 rib fracture with bloody effusion from chest tube; 2) initial chest tube placed ≥36 h of hospital admission. Patients were excluded for hemopneumothoraces. The primary endpoint was having at least one of the following chest tube complications: tube replacement, VATS, tube falling out, tube clogging, pneumonia, retained HTX, pleural empyema. Secondary outcomes included chest tube output volume and drainage rate. Dependent/independent and parametric/non-parametric analyses were used to assess primary and secondary outcomes. RESULTS: There were 160 SB patients (191 tubes) and 60 LB patients (72 tubes). Both comparison groups were similar in multiple demographic, injury, clinical features. The median (IQR) tube size for each group was as follows: SB [12 Fr (12-14)] and LB [32 Fr (28-32)]. The risk of having at least one chest tube complication was similar for LB and SB chest tubes (14% vs. 18%, p = 0.42). LB tubes had significantly larger risk of VATS, while SB tubes had significantly higher risk of pneumonia. SB tubes had significantly slower least squares (LS) mean initial output drainage rate compared to LB tubes (52.2 vs. 213.4 mL/hour, p < 0.001), but a non-parametric analysis suggested no significant difference in median drainage rates between groups 39.7 [23.5-242.0] mL/hr. vs. 38.6 [27.5-53.8], p = 0.81. LB and SB groups had similar initial output volume (738.0 mL vs. 810.9, p = 0.59). CONCLUSIONS: There was no clearly superior chest tube diameter size; both chest tube sizes demonstrated risks and benefits. Clinicians must be aware of these potential tradeoffs when deciding on the diameter of chest tube for the treatment of delayed HTXs.

[Otorhinolaryngology, head and neck surgery in Kenya--consequences of demographic parameters]. / Hals-Nasen-Ohrenheilkunde in Kenia - Auswirkungen demographischer Parameter.

BACKGROUND: In the time of evidence based medicine the analysis of the influence of demographic parameters and different environmental factors on the treatment concepts in a country is often neglected. This is also true for Otorhinolaryngology. METHOD: An evaluation of the situation concerning distribution of physicians, diagnostic procedures and epidemiology in Kenya has been performed. These factors are discussed in consideration of their effect on the incidence of different diseases and their treatment under the specific socio-economic conditions for the otolaryngological situation in Kenya. RESULTS: In Kenya 28 otolaryngologists are registered that concentrate on few urban regions. Chronic otitis media, malignant tumors in the head and neck region and AIDS associated diseases have meanwhile increased dramatically. Numerous instruments and equipment for diagnosis are missing. Bigger equipment for CT scans are nearly exclusively used by private hospitals. PERSPECTIVE: Beside a better provision with different equipment for diagnosis it is especially the organization of certain training programmes where local physicians are further educated that may lead to an optimised medical care in Kenya.

Immune thrombocytopenic purpura during pregnancy: laparoscopic treatment.

BACKGROUND AND OBJECTIVES: Laparoscopic surgical techniques in pregnancy have been accepted and pose minimal risks to the patient and fetus. We present the first reported case of a pregnant woman with immune thrombocytopenia purpura who underwent laparoscopic splenectomy during the second trimester. METHODS AND RESULTS: The anesthesia, hematology, and obstetrics services closely followed the patient's preoperative and intraoperative courses. After receiving immunization, stress close steroids, and prophylactic antibiotics, she underwent a successful laparoscopic splenectomy. After a short hospital stay, the patient was discharged home. CONCLUSION: Immune thrombocytopenia purpura can be an indication for splenectomy. As demonstrated in appendectomy, cholecystectomy, and our case presentation, laparoscopic splenectomy can be safely performed during pregnancy.

Cholestasis confers resistance to the rat liver mitochondrial permeability transition.

BACKGROUND & AIMS: Bile salts can cause hepatocyte death by inducing the mitochondrial permeability transition (MPT). However, the slow progression of human cholestatic liver diseases suggests that hepatocytes adapt to resist the MPT. Bcl-x, a protein, and increased mitochondrial cardiolipin, a membrane lipid, elevate the threshold for the MPT. Our aims were to determine if liver mitochondria become resistant to the MPT during cholestasis and, if so, if the resistance is mediated by Bcl-x and/or increased cardiolipin. METHODS: Hepatocytes and liver mitochondria were obtained from bile duct-ligated (BDL) rats and sham-operated rats (control). RESULTS: After addition of glycochenodeoxycholate (GCDC), the magnitude of the MPT was reduced in mitochondria from BDL rats vs. controls. Although Bcl-xL was not increased, mitochondrial cardiolipin content was significantly greater in BDL rats vs. controls. Cell viability was also increased in hepatocytes from BDL rats vs. controls after treatment with GCDC. Feeding BDL rats a fatty acid-deficient diet prevented the increase in mitochondrial cardiolipin content; mitochondria and hepatocytes from these rats were susceptible to the MPT and hepatocellular death by GCDC. CONCLUSIONS: These data suggest that an increase in mitochondria cardiolipin content occurs during cholestasis as an adaptive phenomenon to resist cell death by the MPT.

Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver. It is, though, a rare tumor and little is known regarding its natural history, clinicopathologic characteristics, or the outcomes of surgical therapy. We reviewed the experience of 61 patients with ICC seen by the surgical service at the Mayo Clinic over a 31-year period. Patient demographic and clinical data were recorded, as were survival statistics. Pathologic data were also obtained and patients stratified according to the TNM classification. Twenty-eight patients were resected for cure. Overall, 45 patients died of ICC. Of the patients resected for cure, survival at 3 years was 60%. No pathologic condition was found to be associated with the development of ICC. Overall survival correlated with stage of the tumor. Among patients resected for cure, stage did not correlate with survival. Prognosis for patients with ICC remains poor; resection, though, appears to prolong survival.

A prospective randomized trial of an antibiotic- and antiseptic-coated central venous catheter in the prevention of catheter-related infections.

OBJECTIVE: To test the efficacy of the ARROWgard (Arrow International Inc, Reading, Pa) central venous catheter (CVC) coated with silver sulfadiazine and chlorhexidine (A-CVC) in the prevention of CVC-related infections. DESIGN: Prospective, randomized trial. SETTING: A tertiary care medical center. PATIENTS AND INTERVENTION: Two hundred eighty-two patients who required CVC placement were evaluated in this study. Patients were prospectively randomized to receive either a standard CVC (S-CVC) or the A-CVC. Only fresh-stick double- and triple-lumen catheters were studied. MAIN OUTCOME MEASURES: Patients were evaluated for catheter site inflammation, catheter site colonization, local catheter-related infection, and catheter-related septicemia. RESULTS: The 2 groups were matched for age, percentage in the intensive care unit, percentage receiving total parenteral nutrition, percentage with triple-lumen catheters, and duration of catheterization. Rates of catheter site inflammation in the 2 groups were similar (12% vs 10%, S-CVC group and A-CVC group, respectively). The A-CVC was associated with a significantly decreased catheter site colonization rate (49% vs 28%; 43% reduction; P<.001) and local catheter-related infection rate (22.4% vs 5.8%; 74% reduction; P<.001). Rates of catheter-related septicemia were reduced by 41% in the A-CVC group (6.4% vs 3.8%, S-CVC group and A-CVC group, respectively), but this was not statistically significant. CONCLUSIONS: Despite a marked decrease in catheter site colonization and catheter-related infection rates, the A-CVC did not significantly reduce the incidence of catheter-related septicemia. This may be due to a greater pathogenic dependence on catheter hub contamination rather than catheter site colonization or local catheter-related infection, or the relatively short (5.2 days) duration of catheterization in this study.

Interferon-gamma primes neutrophil-mediated gastric surface cell cytotoxicity.

The T lymphocyte product interferon-gamma (IFN-gamma) upregulates or primes polymorphonuclear leukocyte (PMN) oxidative responses to the receptor-initiated stimulant N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not to the transduction-mediated stimulant phorbol myristate acetate (PMA). We sought a functional correlation between IFN-gamma-induced oxidative priming of PMNs and PMN-mediated cytotoxicity, using an in vitro assay of 51Cr release from rabbit gastric surface cells. Compared with control PMNs, IFN-gamma-primed PMNs exhibited a significant increase in cytotoxicity when stimulated with FMLP, but not when stimulated with PMA. IFN-gamma-induced, FMLP-stimulated, PMN-mediated cytotoxicity was reduced by adding superoxide dismutase to scavenge superoxide anion or by adding catalase or glutathione peroxidase to scavenge hydrogen peroxide. Cytotoxicity was also reduced by inhibiting myeloperoxidase activity with azide or scavenging HOCl with alanine or methionine. Cytotoxicity was blocked by a monoclonal antibody against the CD11/CD18 integrin of PMNs. The results indicate that the immunoregulatory lymphokine IFN-gamma primes the FMLP-stimulated cytotoxic activity of PMNs via the increased generation of reactive oxygen metabolites and indicate that cytotoxicity may require effector-target cell adherence. Therefore, T lymphocyte-derived IFN-gamma may have a role in the pathogenesis of PMN-mediated injury to gastric and gastrointestinal tract mucosa.

Oxidative priming of neutrophils by interferon-gamma.

Priming of neutrophil (PMN) oxidative responses is an integral component of host defense and inflammation and may contribute to cell-mediated tissue injury. The characteristics and mechanisms of interferon-gamma (IFN-gamma)-induced oxidative priming of PMNs were explored in vitro. Following pretreatment of human PMNs with recombinant IFN-gamma, superoxide anion release was selectively primed toward the receptor-initiated stimulants f-Met-Leu-Phe (fMLP) and C5a but not toward the transduction-mediated stimulants phorbol myristate acetate and A23187, a calcium ionophore. IFN-gamma also induced priming toward the stimulant NaF, a direct activator of guanine nucleotide regulatory proteins. Priming was not associated with changes in fMLP surface receptor expression or degranulation. Priming was dependent on de novo mRNA and protein synthesis. The immuno-regulatory lymphokine IFN-gamma primes PMN oxidative responses, apparently via production of proteins that are involved in the early postreceptor transductional pathways of oxidative metabolism.

Ganglioside GM3 sialidase activity in fibroblasts of normal individuals and of patients with sialidosis and mucolipidosis IV. Subcellular distribution and and some properties.

Sensitive assays for the determination of the ganglioside sialidase activity of fibroblast homogenates were established using ganglioside GM3, 3H-labelled in the sphingosine moiety, as a substrate. Ganglioside GM3 sialidase activity was greatly stimulated by the presence of the non-ionic detergent Triton X-100 and was further enhanced by salts such as NaCl; the optimal pH was 4.5. The subcellular localization of this activity was determined by fractionation using free-flow electrophoresis and found to be exclusively associated with the marker for the plasma membrane, but not with that for lysosomes. This Triton-stimulated ganglioside sialidase activity was selectively inhibited by preincubating intact cells in the presence of millimolar concentrations of Cu2+, suggesting that the activity resides on the external surface of the plasma membrane. In normal fibroblasts homogenates, ganglioside GM3 sialidase was also greatly stimulated by sodium cholate. In contrast to the Triton X-100-activated reaction, however, it was not diminished by prior incubation of intact cells in the presence of Cu2+. Only after cell lysis was Cu2+ inhibitory. the cholate-stimulated ganglioside sialidase activity thus paralleled the behaviour of the lysosomal 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid (4-MU-NeuAc) sialidase. In fibroblasts from sialidosis patients, the cholate-stimulated ganglioside GM3 sialidase activity, but not that of the Triton-activated enzyme, was profoundly diminished. In fibroblasts from patients with mucolipidosis IV (ML IV), both the Triton X-100- and the cholate-stimulated ganglioside GM3 sialidase activities were in the range of normal controls. The Triton-activated enzyme was associated with the plasma membrane in the same manner as in normal cells. Our findings suggest that, in human fibroblasts, there exist two sialidases that degrade ganglioside GM3: one on the external surface of the plasma membrane, and another that is localized in lysosomes and seems identical with the activity that acts on sialyloligosaccharides and 4-MU-NeuAc. As neither activity was found to be deficient in ML IV fibroblasts, our results argue against the hypothesis of a primary involvement of a ganglioside GM3 sialidase in the pathogenesis of ML IV.

Polysomal and cytoplasmic mRNP particles containing 7S(L) RNA.

Nuclear RNP complexes, cytoplasmic mRNP particles and free and membrane-bound polysomes were prepared from rat liver and their low-molecular-mass RNA components were analyzed on polyacrylamide/formamide gels. The separated small RNAs transferred to diazophenylthioether paper were hybridized to the nick-translated recombinant plasmid pA6 containing cDNA sequences for the low-Mr RNA called 7S(L) RNA. Nuclear RNP particles and free and membrane-bound polysomes were found to contain 7S(L) RNA. In the cytoplasm 7S(L) RNA could be identified as the major small RNA in 20-S cmRNP particles.