[Systematic risk management for a planned gas shutdown in the high-care facility of a university hospital]. / Systematisches Risikomanagement für eine geplante Gasabschaltung im High-Care-Bereich eines Universitätsklinikums.

BACKGROUND: In the course of building extension works at Dresden University Hospital, it was necessary to shut down the central medical gas supply in a building with 3 intensive care wards with 22 beds, an operating theater tract with 5 operating rooms and 6 normal wards each with 28 beds during ongoing services. Thus, for the construction phase there was a need to establish an interim decentralized gas supply with zero failure tolerance for the affected functional units . METHODS: Following established procedures for possible risk and failure analysis, a project group was set up by the hospital's emergency and disaster management officer to develop a project plan, a needs assessment and a communication plan. RESULTS: A variety of risk factors were systematically identified for which appropriate countermeasures needed to be designed. The needs assessment over 4 h based on physiological parameters for the maximum available 22 ventilator beds resulted in 26,000 l of oxygen and 26,000 l of compressed air. A total of 7 supply points were each equipped with two 50l cylinders for both oxygen and compressed air, with a total availability of 175,000 l of each of the 2 gases. Another eight cylinders each were held in reserve. The project was carried out on a Saturday without an elective surgery program, so that the operating rooms concerned could be closed. The timing was chosen so that double staffing of intensive care personnel was available during the afternoon shift change. In advance, as many of the patients on mechanical ventilation as possible were transferred within the hospital; however, nine of the mechanically ventilated patients had to remain. The technical intervention in the gas supply lasted only 2 h without affecting the patient's condition. During the 2­h interim supply, 16,500 l of compressed air and 8000 l of oxygen were consumed on the high-care wards. The calculated hourly consumption per ventilated patient was 917 l of air (15 l/min) and 444 l of oxygen (7 l/min). The quantity framework based on empirical values from intensive care medicine was significantly lower. This was more than compensated for by the 10-fold stocking of gas and the predictably lower number of ventilated patients than the maximum occupancy used as a basis. CONCLUSION: For technical interventions in high-risk areas, careful planning and execution in an effective team is required. Established procedures of project management and risk assessment help to avoid errors.

Enhancing Anticoagulation Monitoring and Therapy in Patients Undergoing Microvascular Reconstruction in Maxillofacial Surgery: A Prospective Observational Trial.

BACKGROUND: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) anticoagulation monitoring. This paper describes a protocol for enhanced anticoagulation monitoring during maxillofacial flap surgery. OBJECTIVE: The aim of the study will be to evaluate, in a controlled setting, the predictive value of POC devices for the type of flap perfusion disorders due to thrombosis or bleeding. VET, Platelet monitoring (PM) and standard laboratory tests (SLT) are comparatively examined. METHODS/DESIGN: This study is an investigator-initiated prospective trial in 100 patients undergoing maxillofacial surgery. Patients who undergo reconstructive surgery using microvascular-free flaps will be consecutively enrolled in the study. All patients provide blood samples for VET, PM and SLT at defined time points. The primary outcome is defined as free flap loss during the hospital stay. Statistical analyses will be performed using t-tests, including the Bonferroni adjustment for multiple comparisons. DISCUSSION: This study will help clarify whether VET can improve individualized patient care in reconstruction surgery. A better understanding of coagulation in relation to flap perfusion disorders may allow real-time adaption of antithrombotic strategies and potentially prevent flap complications.

Evaluation of liver fibrosis and cirrhosis on the basis of quantitative T1 mapping: Are acute inflammation, age and liver volume confounding factors?

PURPOSE: To evaluate potential confounding factors in the quantitative assessment of liver fibrosis and cirrhosis using T1 relaxation times. METHODS: The study population is based on a radiology-information-system database search for abdominal MRI performed from July 2018 to April 2019 at our institution. After applying exclusion criteria 200 (59 ±â€¯16 yrs) remaining patients were retrospectively included. 93 patients were defined as liver-healthy, 40 patients without known fibrosis or cirrhosis, and 67 subjects had a clinically or biopsy-proven liver fibrosis or cirrhosis. T1 mapping was performed using a slice based look-locker approach. A ROI based analysis of the left and the right liver was performed. Fat fraction, R2*, liver volume, laboratory parameters, sex, and age were evaluated as potential confounding factors. RESULTS: T1 values were significantly lower in healthy subjects without known fibrotic changes (1.5 T MRI: 575 ±â€¯56 ms; 3 T MRI: 857 ±â€¯128 ms) compared to patients with acute liver disease (1.5 T MRI: 657 ±â€¯73 ms, p < 0.0001; 3 T MRI: 952 ±â€¯37 ms, p = 0.028) or known fibrosis or cirrhosis (1.5 T MRI: 644 ±â€¯83 ms, p < 0.0001; 3 T MRI: 995 ±â€¯150 ms, p = 0.018). T1 values correlated moderately with the Child-Pugh stage at 1.5 T (p = 0.01, ρ = 0.35). CONCLUSION: T1 mapping is a capable predictor for detection of liver fibrosis and cirrhosis. Especially age is not a confounding factor and, hence, age-independent thresholds can be defined. Acute liver diseases are confounding factors and should be ruled out before employing T1-relaxometry based thresholds to screen for patients with liver fibrosis or cirrhosis.

Revisiting DCE-MRI: Classification of Prostate Tissue Using Descriptive Signal Enhancement Features Derived From DCE-MRI Acquisition With High Spatiotemporal Resolution.

METHODS: A retrospective study (from January 2016 to July 2019) including 75 subjects (mean, 65 years; 46-80 years) with 2.5-second temporal resolution DCE-MRI and PIRADS 4 or 5 lesions was performed. Fifty-four subjects had biopsy-proven prostate cancer (Gleason 6, 15; Gleason 7, 20; Gleason 8, 13; Gleason 9, 6), whereas 21 subjects had negative MRI/ultrasound fusion-guided biopsies. Voxel-wise analysis of contrast signal enhancement was performed for all time points using custom-developed software, including automatic arterial input function detection. Seven descriptive parameter maps were calculated: normalized maximum signal intensity, time to start, time to maximum, time-to-maximum slope, and maximum slope with normalization on maximum signal and the arterial input function (SMN1, SMN2). The parameters were compared with ADC using multiparametric machine-learning models to determine classification accuracy. A Wilcoxon test was used for the hypothesis test and the Spearman coefficient for correlation. RESULTS: There were significant differences (P < 0.05) for all 7 DCE-derived parameters between the normal peripheral zone versus PIRADS 4 or 5 lesions and the biopsy-positive versus biopsy-negative lesions. Multiparametric analysis showed better performance when combining ADC + DCE as input (accuracy/sensitivity/specificity, 97%/93%/100%) relative to ADC alone (accuracy/sensitivity/specificity, 94%/95%/95%) and to DCE alone (accuracy/sensitivity/specificity, 78%/79%/77%) in differentiating the normal peripheral zone from PIRADS lesions, biopsy-positive versus biopsy-negative lesions (accuracy/sensitivity/specificity, 68%/33%/81%), and Gleason 6 versus ≥7 prostate cancer (accuracy/sensitivity/specificity, 69%/60%/72%). CONCLUSIONS: Descriptive perfusion characteristics derived from high-resolution DCE-MRI using model-free computations show significant differences between normal and cancerous tissue but do not reach the accuracy achieved with solely ADC-based classification. Combining ADC with DCE-based input features improved classification accuracy for PIRADS lesions, discrimination of biopsy-positive versus biopsy-negative lesions, and differentiation between Gleason 6 versus Gleason ≥7 lesions.

Validation of a Manual Protocol for BRAF V600E Mutation-specific Immunohistochemistry.

Detection of BRAF V600E has diagnostic, prognostic, and therapeutic relevance. The recently developed BRAF V600E mutation-specific antibody has evolved into a feasible alternative to DNA analysis. The plethora of immunohistochemical protocols makes implementation tedious and, here we tested a set of manual and automated protocols and compared test performance with sequencing results. For assays, we employed formalin-fixed, in part decalcified, and paraffin-embedded tissue samples. Empiric testing of manual protocols included 10 variables in 17 protocols. Automated immunohistochemical staining and BRAF pyrosequencing served as independent test methods. Test performance measures were compared without considering 1 method as a standard. Four well-fixed samples (2WT/2Mut) were used for testing of all protocols and indicated 2 correctly classifying procedures. Practical performance assessment employed 33 independent tissue samples, composed of 27 leukemias (by pyrosequencing: 8 wild-type; 18 mutated; 1 noninformative) and 6 melanomas (V600E; V600K; wild-type, 2 each). Manual V600E staining was positive in 20 cases (19 of 20 V600E-containing samples plus the 1 sample that was noninformative), whereas all wild-type and V600K cases were immunonegative. Manual or automated staining as well as pyrosequencing would have missed an equal number of V600E-mutated cases and the correlation coefficient for these methods was 0.75 to 0.93 (substantial to almost perfect); the Youden index was 0.95. Detection of V600E-mutated BRAF at the protein level in routine and decalcified tissue samples is possible, and the presented manual protocols should expedite implementation in routine diagnostic practice. Our results indicate that both molecular techniques should be considered complementary.

Is there value for serial ultrasonographic assessment of cervical lengths after a cerclage?

OBJECTIVE: The objective of the study was to determine the value of serial ultrasonographic cervical length (CL) measurements after cerclage to predict preterm delivery. STUDY DESIGN: Retrospective ultrasonographic and outcome data from singleton pregnancies with cerclage were reviewed. Using transvaginal ultrasound (TVS), overall CL obtained before cerclage placement, 2 weeks after cerclage, and before delivery were compared between women who delivered preterm (less than 37 weeks) and term. The overall CL including CL above (CLA) and below the cerclage (CLB) were compared using the SAS program. RESULTS: Cerclage was placed at 15.7 +/- 3.6 weeks (mean +/- SD) in 57 women. The overall CL before cerclage, 2 weeks after cerclage, and the last TVS before delivery was not different in preterm and term births. The odds ratio of a measurable CLA for preterm delivery by TVS was 0.87 (0.78 to 0.95, 95% confidence interval). Thirty-two patients (56%) had absent CLA at 26.7 +/- 4.4 weeks. Of these, 16 (50%) were delivered for preterm premature rupture of membranes (PPROM) and chorioamnionitis (sensitivity of 100%, specificity of 61%, positive predictive value of 50%, and negative predictive value of 100%). CONCLUSION: Although the overall cervical length by serial TVS after cerclage did not predict preterm birth, absent CLA is associated with preterm delivery, chorioamnionitis, and PPROM.

Topodiagnostic implications of hemiataxia: an MRI-based brainstem mapping analysis.

The topodiagnostic implications of hemiataxia following lesions of the human brainstem are only incompletely understood. We performed a voxel-based statistical analysis of lesions documented on standardised MRI in 49 prospectively recruited patients with acute hemiataxia due to isolated unilateral brainstem infarction. For statistical analysis individual MRI lesions were normalised and imported in a three-dimensional voxel-based anatomical model of the human brainstem. Statistical analysis revealed hemiataxia to be associated with lesions of three distinct brainstem areas. The strongest correlation referred to ipsilateral rostral and dorsolateral medullary infarcts affecting the inferior cerebellar peduncle, and the dorsal and ventral spinocerebellar tracts. Secondly, lesions of the ventral pontine base resulted in contralateral limb ataxia, especially when ataxia was accompanied by motor hemiparesis. In patients with bilateral hemiataxia, lesions were located in a paramedian region between the upper pons and lower midbrain, involving the decussation of dentato-rubro-thalamic tracts. We conclude that ataxia following brainstem infarction may reflect three different pathophysiological mechanisms. (1) Ipsilateral hemiataxia following dorsolateral medullary infarctions results from a lesion of the dorsal spinocerebellar tract and the inferior cerebellar peduncle conveying afferent information from the ipsilateral arm and leg. (2) Pontine lesions cause contralateral and not bilateral ataxia presumably due to major damage to the descending corticopontine projections and pontine base nuclei, while already crossed pontocerebellar fibres are not completely interrupted. (3) Finally, bilateral ataxia probably reflects a lesion of cerebellar outflow on a central, rostral pontomesencephalic level.

Medullary infarcts may cause ipsilateral masseter reflex abnormalities.

There is a suprasegmental influence on the masseter reflex (MassR) in animals, which is mediated via the fifth nerve spinal nucleus (5SpN). Corresponding data in humans are lacking. Out of 268 prospectively recruited patients with clinical signs of acute brainstem infarctions, we identified 38 with magnetic resonance imaging (MRI)-documented unilateral infarcts caudal to the levels of the fifth nerve motor and main sensory nuclei. All had biplanar T2- and echo planar diffusion-weighted MRI and MassR testing. Five patients (13%) had ipsilateral MassR abnormalities. In all, the infarcts involved the region of the 5SpN. Patients with medullary infarcts involving the region of the 5SpN may thus have ipsilateral MassR abnormalities. This possibly represents an interruption of an excitatory projection mediated via the 5SpN to masseter motoneurons in the fifth nerve motor nucleus. MassR abnormalities with medullary lesions restrict the topodiagnostic value of the MassR.

Concentrations of persistent organochlorine contaminants in bowhead whale tissues and other biota from northern Alaska: implications for human exposure from a subsistence diet.

Bowhead whale (Balaena mysticetus; n = 5) blubber, liver, muscle, kidney, heart, diaphragm, tongue, and uncooked maktak (bowhead whale epidermis and blubber) were collected during subsistence hunts at Barrow, AK, USA (1997-1999) to measure concentrations of persistent organochlorine contaminants (OCs). The exposure of humans to OCs via bowhead whales and other biota [fish, ringed (Phoca hispida) and bearded seals (Erignathus barbatus), and beluga whale (Delphinapterus leucas)] as part of a subsistence diet was evaluated. Concentrations of OCs in bowhead whale tissues were correlated with lipid content (P < 0.001) and were less than levels in other marine mammals reported herein, reflecting the lower trophic status of this cetacean. The relative proportions of hexachlorobenzene (HCB) and sum (Sigma) concentrations of chlordane components (SigmaCHL), DDT-related compounds (SigmaDDT), and polychlorinated biphenyls (SigmaPCB) were not statistically different among the tissues analyzed (P < 0.05). However, relatively higher proportions of hexachlorocyclohexane isomers (SigmaHCH), particularly beta-HCH, were observed in bowhead whale heart and diaphragm (P < 0.03). Based on Canadian and World Health Organization daily intake guidelines, "safe" human consumption rates of bowhead whale tissue and other marine biota were calculated. The most restrictive limits (mean value) for daily consumption for bowhead and beluga whale were 302 and 78 g for maktak and maktaaq (beluga whale epidermis and blubber), respectively. The tolerable daily intake limits of dioxin-like compounds from the consumption of bowhead whale blubber and liver were calculated to be 199 g (approximately 600 g for maktak) and 2222 g, respectively. A detailed profile of traditional/country foods consumed by subsistence communities of northern Alaska is required to address chronic exposure in more detail. Overall, bowhead whale tissues and other biota from northern Alaska are safe to consume at, or below, the levels calculated.

Somatotopic organization of the corticospinal tract in the human brainstem: a MRI-based mapping analysis.

To investigate the incompletely understood somatotopical organization of the corticospinal tract in the human brainstem, we performed a voxel-based statistical analysis of standardized magnetic resonance scans of 41 prospectively recruited patients with pyramidal tract dysfunction caused by acute brainstem infarction. Motor hemiparesis was rated clinically and by the investigation of motor evoked potentials to arms and legs. Infarction affected the pons in 85% of cases. We found the greatest level of significance of affected brainstem areas between the pontomesencephalic junction and the mid pons. Lesion location was significantly more dorsal in patients with hemiparesis affecting more proximal muscles and was significantly more ventral in patients with predominantly distal limb paresis. Comparison of magnetic resonance lesion from patients with paresis predominantly affecting arm or leg did not show significant topographical differences. We conclude that a topographical arm/leg distribution of corticospinal fibers is abruptly broken down as the descending corticospinal tract traverses the pons. Corticospinal fibers, however, follow a somatotopical order in the pons with fibers controlling proximal muscles being located close to the reticular formation in the dorsal pontine base, and thus more dorsal than the fibers controlling further distal muscle groups.

A retrospective review of isoimmunized pregnancies managed by middle cerebral artery peak systolic velocity.

OBJECTIVE: The purpose of this study was to determine the clinical outcome of isoimmunized pregnancies managed primarily by middle cerebral artery peak systolic velocity. STUDY DESIGN: A retrospective chart review was conducted of isoimmunized pregnancies that underwent ultrasound examinations from January 1, 2001, through May 1, 2003. Ultrasound reports, laboratory tests, and maternal and neonatal charts were reviewed. RESULTS: Women with a clinically significant red blood cell antibody and titer value were included. The study population consisted of 39 women (40 pregnancies, 42 fetuses). Patients with a middle cerebral artery peak systolic velocity of > or =1.5 MoM were offered amniocentesis. Seven pregnancies had an abnormal middle cerebral artery peak systolic velocity. Three of these infants had significant anemia. Six of the 7 pregnancies required an exchange transfusion. None of the 33 pregnancies (35 neonates) with normal middle cerebral artery peak systolic velocity measurements resulted in a neonate with significant anemia or severe hyperbilirubinemia. CONCLUSION: The clinical outcome of these pregnancies supports the use of middle cerebral artery peak systolic velocity measurements in the management of isoimmunized pregnancies.

Seventh nerve palsies may be the only clinical sign of small pontine infarctions in diabetic and hypertensive patients.

BACKGROUND: Small brainstem infarctions are increasingly recognized as a cause of isolated ocular motor and vestibular nerve palsies in diabetic and/or hypertensive patients. This raises the question whether there are also isolated 7(th) nerve palsies due to pontine infarctions in patients with such risk factors for the development of cerebrovascular diseases. METHODS: Over an 11-year-period, we retrospectively identified 10 diabetic and/or hypertensive patients with isolated 7(th) nerve palsies and electrophysiological abnormalities indicating pontine dysfunction. All patients had examinations of masseter and blink reflexes, brainstem auditory evoked potentials, direct current electro-oculography including bithermal caloric testing, and T1- and T2-weighted MRI (slice thickness: 4-7 mm). RESULTS: Electrophysiological abnormalities on the side of the 7(th) nerve palsy included delayed masseter reflex latencies (4 patients), slowed abduction saccades (4 patients), vestibular paresis (2 patients), and abnormal following eye movements (2 patients). Electrophysiological abnormalities were always improved or normalized at re-examination, which was always associated with clinical improvement. MRI revealed an ipsilateral pontine infarction in 2 patients. Another 2 had bilateral hyperintense intrapontine lesions, and one an ipsilateral cerebellar infarction. CONCLUSIONS: Simultaneous improvement or recovery of abnormal clinical and electrophysiological findings strongly indicated that both were caused by the same actual pontine lesions. A 7(th) nerve palsy may be the only clinical sign of a pontine infarction in diabetic and/or hypertensive patients. Such mechanism may be underestimated if based on MRI only.

Electrophysiological brainstem testing in the diagnosis of reversible brainstem ischemia.

The aim of this study was to evaluate the sensitivity of multimodal electrophysiological brainstem testing in the diagnosis of clinically suspected reversible ischemic deficits of the brainstem compared with diffusion weighted MR imaging. We investigated 158 consecutive patients presenting with signs of acute brainstem dysfunction. Serial electrophysiological brainstem tests including masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the oculoauricular phenomenon were applied. In 14 of the 158 patients neurological deficits resolved in less than 24 hours, which was suggestive of a transitory ischemic attack (TIA), 19 patients had brainstem signs for more than 24 hours but less than 1 week, suggestive of a reversible ischemic neurological deficit (RIND). Electrophysiological data indicated acute functional brainstem lesions in 54,5 % of patients with transient clinical brainstem impairment. Lesion detection rate was significantly higher when combining electrophysiological data and MRI (60,4 %) than using acute brainstem abnormalities in diffusion weighted MRI alone (39,4 %). We conclude that diffusion weighted MRI and electrophysiological brainstem testing are complimentary sensitive indicators of acute brainstem lesions in patients with reversible neurological deficits. Correct identification of brainstem ischemia influences the therapeutic regimen and may improve patient outcome.

Low-frequency ultrasound induces nonenzymatic thrombolysis in vitro.

OBJECTIVE: To evaluate whether ultrasound, applied over a distance of several centimeters and in the absence of thrombolytic agents, may have a thrombolytic effect on blood clots. METHODS: Low-frequency (20 kHz) continuous wave ultrasound at different intensity levels (0.15-1.2 W/cm2) and exposure times (5, 10, and 20 minutes) was assessed for its potential to induce thrombolysis of fresh human blood clots. The ultrasound effect was also studied in combination with recombinant tissue-type plasminogen activator-mediated thrombolysis. Experiments were carried out in a flow model in degassed sodium phosphate buffer at 37 degrees C at a distance of 3 cm from the ultrasonic probe to the blood clots. Regardless of ultrasound exposure times, blood clots in all experimental groups and the control group were left in the flow system for 20 minutes. RESULTS: The use of ultrasound alone showed a significant thrombolytic effect compared with the control group, with a statistically significant effect at 0.15 W/cm2 and exposure of 10 minutes (P = .02). There was a clear correlation between the extent of weight loss and the chosen intensity level and exposure time. Complete disruption in 8 of 10 blood clots occurred at 1.2 W/cm2 within 10 min. Addition of ultrasound to recombinant tissue-type plasminogen activator-mediated thrombolysis significantly enhanced thrombolysis compared with application of recombinant tissue-type plasminogen activator or ultrasound alone (P = .0001), with the results pointing toward a purely additive, nonsynergistic effect of the 2 treatment modalities. Lysis was more effective in fresh thrombi. CONCLUSIONS: The use of low-frequency ultrasound alone, without addition of a thrombolytic drug, has the potential to induce thrombolysis over a distance. Combination of ultrasound with recombinant tissue-type plasminogen activator is superior to either treatment alone. Ultrasound is a promising tool for developing an alternative or additional treatment modality for acute cerebral vessel occlusion.

Nongenomic cardiovascular effects of triiodothyronine in euthyroid male volunteers.

T(3) has been shown to exert cardiovascular effects. These effects have not yet been defined with regard to the mode of action (nongenomic vs. genomic) and with regard to an interaction with the adrenergic system in humans. To address these issues we conducted a randomized, double blind, 6-fold cross-over trial in 18 healthy male volunteers. After pretreatment with the beta-agonist dobutamine, the beta-blocking agent esmolol, or placebo (0.9% NaCl), 100 microg T(3) or placebo were injected. Primary target variables were systemic vascular resistance (SVR) and cardiac output (CO) within 45 min after injection of T(3) vs. placebo after placebo pretreatment. Sympatho-vagal balance was assessed by measurement of heart rate variability. T(3) caused a lower SVR and a higher CO than placebo (P < 0.001) after pretreatment with placebo. An increased low frequency (LF)/high frequency (HF) ratio (power in LF/power in HF band) after T(3) compared with placebo (P = 0.004) suggests an increase in sympathetic tone. After pretreatment with dobutamine, the effects of T(3) on SVR and CO were abolished, and the effect on LF/HF ratio was reversed. After pretreatment with esmolol, the effects on SVR and LF/HF ratio were reversed. Our data show, for the first time, nongenomic cardiovascular effects of T(3) in humans.

Fractured mandible and associated oral lesions in a subsistence-harvested bowhead whale (Balaena mysticetus).

A fractured right mandible with midlength nonunion and oral lesions were noted in a subsistence-harvested female bowhead whale (Balaena mysticetus) near Wainwright, Alaska (USA). The cause of the fracture was not apparent. The fracture resulted in misalignment of the mandible. The abnormal mobility at the fracture site probably caused irregular baleen stowage within the oral cavity, leading to breakage of many baleen plates and extensive ulceration of the tongue and lips. Good body condition suggested the fracture was not debilitating.