The "fallen lung with absent hilum" signs of complete bronchial transection

A 19-year-old pedestrian who was the victim of a motor vehicle accident had a left pneumothorax with a large air leak. Despite a well-placed chest tube, a chest radiograph showed that the left lung had fallen down and away from the mediastinum and that no hilar structures were visible. This "fallen lung with an absent hilum" is considered virtually diagnostic of complete mainstem bronchus transection.     

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry

Aims

We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke.

Methods

The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke.

Results

At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA₂DS₂-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05–7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04–10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24–9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01–0.47, P < 0.01; n = 56], CHA₂DS₂-VASc score [OR per point 1.47, 95% CI 1.08–2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28–2.84, P < 0.01].

Conclusion

At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.

Clinical trial registration

NCT02306824.

     

The critical path method to analyze and modify OR-workflow: integration of an image documentation system.

Intraoperative image documentation is becoming more and more important for quality management in medicine, in terms of forensic documentation, research and teaching. Up to now, no software-based OR-image-documentation system fits satisfactorily into an OR-workflow. The objective of this study is to transparently show system integration in a clinical workflow for evaluating demands on future system developments. An example of the OR-workflow is presented for the department of obstetrics and gynecology at the University of Tuebingen (Germany). Twelve representative gynecologic laparoscopic surgeries were analyzed by using the critical path method (CPM). CPM network diagrams are shown for an actual laparoscopic workflow and for a workflow including an OR-image-documentation system. With the objective not to increase the total time of actual workflow, the maximum system operation time can be calculated for each period of time. Before surgery the maximum system operation time is x(max) = 7,3 minutes. After surgery it has to be assumed that system operation will increase total workflow time. Using the CPM to analyze requirements for system integration in a medical workflow has not yet been investigated. It is an appropriate method to transparently show integration possibilities and to define workflow-based requirements for the development process of new systems.     

Cervical osteomyelitis due to i.v. heroin use: radiologic findings in 14 patients

We reviewed the radiographs of 14 patients who had cervical osteomyelitis and were IV heroin users. Eleven were men and three were women. Their age range was 33-48 years (mean, 39 years). Eleven regularly used the jugular vein access, and three alternated between the jugular and femoral veins. Initial radiographs of the cervical spine in 13 patients showed destruction of two or more vertebral bodies and the adjacent intervertebral disk, as well as a prevertebral soft-tissue mass. In one patient, findings on initial radiographs were normal, but marked destruction at two contiguous intervertebral levels and a large prevertebral abscess were identified 2 weeks later. All the patients had positive results on cultures of joint aspirates or bone biopsy materials (10 patients) or blood (four patients). Ten grew Staphylococcus aureus; two, Staphylococcus epidermidis; one, Streptococcus viridans; and one, Pseudomonas aeruginosa. CT in nine patients showed inflammatory reaction adjacent to the carotid sheath resulting from the repeated jugular injections and delineated the extent of prevertebral abscess and bone destruction. Scintigrams were of minimal value in establishing the diagnosis. Advanced vertebral body destruction, disk space infection, prevertebral abscess, and anterior cervical inflammatory reaction appear to be typical findings on radiographs in heroin abusers with cervical osteomyelitis.     

A touch of humanity

HIV-positive children and women who have been raped in a central Africa war zone are given free care at charity health centres, where local nurses receive training on the job. Staff themselves risk being attacked by armed groups and their pay and resources are limited.     

Regulation resistance

Nurses in France are unhappy with their working conditions and have responded with suspicion to a new body set up to regulate them. The Ordre National des Infirmiers has struggled to attract registrants, but there are signs of improvement.     

From the Cover: Developmental origins of the world’s largest flowers,Rafflesiaceae

Rafflesiaceae, which produce the world’s largest flowers, have captivated the attention of biologists for nearly two centuries. Despite their fame, however, the developmental nature of the floral organs in these giants has remained a mystery. Most members of the family have a large floral chamber defined by a diaphragm. The diaphragm encloses the reproductive organs where pollination by carrion flies occurs. In lieu of a functional genetic system to investigate floral development in these highly specialized holoparasites, we used comparative studies of structure, development, and gene-expression patterns to investigate the homology of their floral organs. Our results surprisingly demonstrate that the otherwise similar floral chambers in two Rafflesiaceae subclades, Rafflesia and Sapria, are constructed very differently. In Rafflesia, the diaphragm is derived from the petal whorl. In contrast, in Sapria it is derived from elaboration of a unique ring structure located between the perianth and the stamen whorl, which, although developed to varying degrees among the genera, appears to be a synapomorphy of the Rafflesiaceae. Thus, the characteristic features that define the floral chamber in these closely related genera are not homologous. These differences refute the prevailing hypothesis that similarities between Sapria and Rafflesia are ancestral in the family. Instead, our data indicate that Rafflesia-like and Sapria-like floral chambers represent two distinct derivations of this morphology. The developmental repatterning we identified in Rafflesia, in particular, may have provided architectural reinforcement, which permitted the explosive growth in floral diameter that has arisen secondarily within this subclade.It has been long recognized that parasitism elicits fundamental changes to an organism’s body plan (1, 2). Similarly, extreme changes in body size can result in dramatic morphological modifications, which in some cases rise to the level of what we term “novelty’” (3–5). Either of these circumstances can pose challenges to understanding structural homology. One lineage that exhibits both complications is the holoparasitic plant family Rafflesiaceae, which produces the world’s largest flowers. Despite their fame, however, the developmental basis of these giants has remained a mystery for nearly two centuries (6, 7). Their floral structure, in particular, is highly modified with respect to most angiosperms, so much so that confusion over their flowers has resulted in Rafflesiaceae-centric terminology to evade statements of homology. This uncertainty has obscured our understanding of their evolutionary origin, which until recently has been unknown (8–10).Most members of the family possess a large, bowl-shaped floral chamber [sometimes referred to as a chamber blossom by pollination biologists (11, 12)]. The floor and walls of this chamber are formed by a perianth tube and the roof is defined by an organ called the diaphragm (Fig. 1 and Fig. S1 A and C–E). The opening of the diaphragm serves as the entrance for carrion fly pollinators (13, 14). The chamber is in turn surrounded by a series of attractive sterile organs, termed perianth lobes (Fig. 1 and Fig. S1 A, C–E, and G–K). The central part of the chamber accommodates the central column, which expands distally to form a disk bearing the reproductive organs (Fig. 1 and Fig. S1). Like their closest relatives, Euphorbiaceae, the flowers of Rafflesiaceae are typically unisexual (9). In female flowers, a stigmatic belt forms around the underside of the reproductive disk (13); in male flowers this is where the stamens are borne.Open in a separate windowFig. 1.Gross morphology, longitudinal sections, and accepted phylogenetic relationships of Rafflesiaceae. Rafflesia (A) and Sapria (C) exhibit floral chambers, defined by a diaphragm, where the central reproductive column resides. The central column of Rhizanthes (B) is exposed because no floral chamber is formed. (Scale bars, ∼2 cm.) Photo credits: (A) D. Boufford, (B) C.C.D., (C) L.A.N.Each of the three genera of Rafflesiaceae produces flowers that vary on this general theme. Rafflesia and Sapria have a similar floral architecture, but differ in their perianths: Rafflesia has one whorl of five perianth lobes (Fig. 1A) and Sapria has two whorls (Fig. 1C), each with five similar lobes. Because of the striking similarity in floral morphology of these two genera, which represent the bulk of species diversity in the family, their floral chambers have been assumed to have originated once in the common ancestor of Rafflesiaceae (15) (Fig. 1). The exception is the species-poor clade Rhizanthes, which lacks the floral chamber found in most Rafflesiaceae (16) (Fig. 1B). Rhizanthes has 16 similar perianth lobes and does not form a diaphragm or chamber closure as in Rafflesia and Sapria. The perianth lobes in Rhizanthes also differ considerably in morphology: they are much narrower, have elaborate hairy “pads,” and terminate with distinct tail-like appendages (Fig. 1 and Fig. S1 G–K). Based on its more nested phylogenetic placement within the family, it has been assumed that the morphology of Rhizanthes is uniquely derived (15). The unusual floral organs of Rafflesiaceae pose a serious challenge to understanding their homology and, thus, their evolution.Like so many branches in the Tree of Life, Rafflesiaceae are not amenable to traditional genetic manipulation, even less so than most plants. These holoparasites grow vegetatively inside their hosts and lack obvious leaves, stems, and roots. The plants have never been successfully propagated, and do not occur outside of their host range in the rainforests of Southeast Asia. Under these circumstances, only multiple independent lines of inquiry can be used to understand the floral structure and evolution of these charismatic plants, including comparative structural, developmental, and gene-expression data. In terms of this last source of data, the ABC model of floral development provides a predictive framework for understanding the identities of the floral organs of Rafflesiaceae (17, 18). The model involves three gene activities: A activity alone specifies sepal identity, A+B define petals, B+C confer stamen identity, and C determines carpel identity. Although it has been recognized that some aspects of the ABC model do not apply to all angiosperms (19), the specification of petal, stamen, and carpel identity by B- and C-class genes is generally conserved in core eudicots (20). In general, great care must be taken when using gene-expression patterns as criteria for establishing homology (21); however, when such correlative data are combined with explicit phylogenetic and developmental data, this approach has been shown to provide critical insights into organ homology (e.g., ref. 22). Along these lines, we cloned homologs of the ABC class genes, which largely belong to the pan-eukaryotic MADS-box (after the four founding members of the family: MCM1, AGAMOUS, DEFICIENS, and SRF) gene family (20), from Rafflesiaceae and studied their expression in different floral organs. We complemented these analyses with an investigation of floral organ initiation and development in all three genera in the family.Our analyses surprisingly demonstrate that the otherwise similar floral chambers in Rafflesia and Sapria are constructed very differently. In Rafflesia, the diaphragm is derived from the petal whorl, whereas normal petals are absent. In contrast, in Sapria the diaphragm is derived from elaboration of a unique ring structure located between the perianth and the stamen whorl. This structure is analogous to sterile organs that have been independently derived in other angiosperms, such as the trumpet in daffodils (23) and the corona in passionflowers (24). The structure is not present in the closest relatives of Rafflesiaceae, and is elaborated to varying degrees in all three genera of Rafflesiaceae. Thus, the structures that define these similar floral chambers are not homologous. In Rhizanthes, which lacks a diaphragm, a derivative of the ring primordium appears to be adnate to the perianth. The development of this organ is more similar to that of Sapria, and is likely a shared symplesiomorphic feature in these two genera. These differences in construction among the three genera refute the simplistic scenario in which the similarities between Sapria and Rafflesia are interpreted as ancestral in the family.