Hypoplastic femur with pathologic femoral shaft fracture associated with extensive arteriovenous malformations. A series of five cases.

Introduction: Extremities arteriovenous malformations are uncommon vascular lesions that usually go unnoticed until a fracture occurs or imaged for other medical problems. The lesion is invariably quiescent, infiltrative in nature, and leads to the destruction of soft tissue and bone. Worldwide 20-30 % incidence of arteriovenous malformations has been noted in bones. This arteriovenous malformation greatly affects bone growth as compared to the normal side and leads to pathological fracture. However, few reports on the management of such pathologic fractures associated with AVM have been published in the literature.The main problem is to decide the types of implants and whether open or closed reduction. Here, we present a case series of pathologic femoral shaft fracture associated with multiple hemangiomas in the thigh that was treated successfully by minimally invasive distal femoral locking plate fixation and teriparatide. Case Presentation: We are describing our one index case. A 39-year-old woman, otherwise healthy, sustained a fall and developed a left femoral shaft fracture. At the time of admission, she had swelling and venous varicosities and non-itchy, blanchable violet patches over the left thigh. Plain radiography of the left thigh revealed Hypoplastic femoral shaft with a markedly obliterated medullary canal with distal 1/3 rd fracture with calcification of soft tissue. We planned open reduction and distal locking femoral plating because medullary canal was very small to accommodate intramedullary nail following embolization of the feeding artery. While performing open reduction, a considerable amount of bleeding (1300 ml) after incision of subcutaneous tissue occurred. After successful fracture fixation, union was achieved with administration of teriparatide 12 months postoperatively. At present patient is able to walk using elbow support. Conclusion: We present the five cases of pathologic fracture associated with large AVMs that achieved fracture union using minimally invasive distal femoral locking plate fixation and teriparatide.

Senescence: Pathogenic Driver in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is recognized as a disease of accelerated lung aging. Over the past two decades, mounting evidence suggests an accumulation of senescent cells within the lungs of patients with COPD that contributes to dysregulated tissue repair and the secretion of multiple inflammatory proteins, termed the senescence-associated secretory phenotype (SASP). Cellular senescence in COPD is linked to telomere dysfunction, DNA damage, and oxidative stress. This review gives an overview of the mechanistic contributions and pathologic consequences of cellular senescence in COPD and discusses potential therapeutic approaches targeting senescence-associated signaling in COPD.

Airway Resistance Caused by Sphingomyelin Synthase 2 Insufficiency in Response to Cigarette Smoke.

Sphingomyelin synthase is responsible for the production of sphingomyelin (SGM), the second most abundant phospholipid in mammalian plasma, from ceramide, a major sphingolipid. Knowledge of the effects of cigarette smoke on SGM production is limited. In the present study, we examined the effect of chronic cigarette smoke on sphingomyelin synthase (SGMS) activity and evaluated how the deficiency of Sgms2, one of the two isoforms of mammalian SGMS, impacts pulmonary function. Sgms2-knockout and wild-type control mice were exposed to cigarette smoke for 6 months, and pulmonary function testing was performed. SGMS2-dependent signaling was investigated in these mice and in human monocyte-derived macrophages of nonsmokers and human bronchial epithelial (HBE) cells isolated from healthy nonsmokers and subjects with chronic obstructive pulmonary disease (COPD). Chronic cigarette smoke reduces SGMS activity and Sgms2 gene expression in mouse lungs. Sgms2-deficient mice exhibited enhanced airway and tissue resistance after chronic cigarette smoke exposure, but had similar degrees of emphysema, compared with smoke-exposed wild-type mice. Sgms2-/- mice had greater AKT phosphorylation, peribronchial collagen deposition, and protease activity in their lungs after smoke inhalation. Similarly, we identified reduced SGMS2 expression and enhanced phosphorylation of AKT and protease production in HBE cells isolated from subjects with COPD. Selective inhibition of AKT activity or overexpression of SGMS2 reduced the production of several matrix metalloproteinases in HBE cells and monocyte-derived macrophages. Our study demonstrates that smoke-regulated Sgms2 gene expression influences key COPD features in mice, including airway resistance, AKT signaling, and protease production.

Cigarette smoke exposure reduces leukemia inhibitory factor levels during respiratory syncytial viral infection.

Background: Viral infections are considered a major driving factor of chronic obstructive pulmonary disease (COPD) exacerbations and thus contribute to disease morbidity and mortality. Respiratory syncytial virus (RSV) is a frequently detected pathogen in the respiratory tract of COPD patients during an exacerbation. We previously demonstrated in a murine model that leukemia inhibitory factor (LIF) expression was increased in the lungs during RSV infection. Subduing LIF signaling in this model enhanced lung injury and airway hypersensitivity. In this study, we investigated lung LIF levels in COPD patient samples to determine the impact of disease status and cigarette smoke exposure on LIF expression. Materials and methods: Bronchoalveolar lavage fluid (BALF) was obtained from healthy never smokers, smokers, and COPD patients, by written informed consent. Human bronchial epithelial (HBE) cells were isolated from healthy never smokers and COPD patients, grown at the air-liquid interface and infected with RSV or stimulated with polyinosinic:polycytidylic acid (poly (i:c)). Mice were exposed to cigarette smoke daily for 6 months and were subsequently infected with RSV. LIF expression was profiled in all samples. Results: In human BALF, LIF protein was significantly reduced in both smokers and COPD patients compared to healthy never smokers. HBE cells isolated from COPD patients produced less LIF compared to never smokers during RSV infection or poly (i:c) stimulation. Animals exposed to cigarette smoke had reduced lung levels of LIF and its corresponding receptor, LIFR. Smoke-exposed animals had reduced LIF expression during RSV infection. Two possible factors for reduced LIF levels were increased LIF mRNA instability in COPD epithelia and proteolytic degradation of LIF protein by serine proteases. Conclusions: Cigarette smoke is an important modulator for LIF expression in the lungs. Loss of LIF expression in COPD could contribute to a higher degree of lung injury during virus-associated exacerbations.

Knowledge about Informed Consent among Doctors of Various Specialities: A Pilot Survey.

BACKGROUND: Informed consent is an integral part of clinical practice. Improper informed consent can lead to mistrust between doctors and patients as well as medico-legal issues. Awareness and knowledge of various aspects of consent is essential in present day medical practice. METHODS: A paper and web-based survey was undertaken to evaluate knowledge about informed consent among doctors. A law and a medical student generated a list of questions based upon available case laws and legislations which were further validated by experts. 500 doctors undertook the survey and of these 457 completed the survey of 18 questions. Both univariate and multivariate models were used to analyze responses. RESULTS: 413 complete questionnaires were included in the analysis. The proportion of respondents furnishing correct responses varied between 49.6% and 93.7%. There were 9 questions for which, over 25% respondents provided inappropriate responses. The questions included those enquiring whether initial consent for diagnostic or therapeutic procedures could apply to extended procedures or surgery and who was capable of giving consent for different procedures. There were significant differences of knowledge between residents and consultants for few questions. The physicians fared worse than surgeons and anesthetists although the difference was not statistically significant. CONCLUSION: Significant knowledge gaps were identified. There were deficiencies in providing correct response particularly in practical scenarios. There is a need to include knowledge about different aspects of informed consent in the medical curriculum.

Treatment of postmenopausal osteoporosis.

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and hence susceptibility to fracture. Calcium and vitamin D are the most commonly used therapies for osteoporosis, although their efficacy in osteoporotic fracture prevention remains uncertain. Biphosphonates are the most frequently prescribed medication for treatment of osteoporosis and are often considered as first-line therapy for the treatment of osteoporosis. Currently, hormone replacement therapy is only approved by the Food and Drug Administration (FDA) for short-term treatment of severe postmenopausal symptoms with the lowest dose used for the shortest time. In view of its lack of effect on the prevention of nonvertebral fractures, the use of raloxifene should be limited to women with spinal osteoporosis. Most experts agree that it is preferable to treat osteoporosis with a more potent agent than calcitonin and manage the pain separately. Currently, the FDA recommends the use of parathyroid hormone for treatment of osteoporosis for a maximum of 2 years because of the concern of development of osteosarcoma.

Atherosclerotic vascular disease may be associated with osteoporosis or osteopenia in postmenopausal women: a preliminary study.

The objective of this study was to determine if there is an association between osteoporosis or osteopenia and atherosclerotic vascular disease (AVD) (two conditions quite prevalent in nursing homes) in a sample of postmenopausal women. We conducted a retrospective chart review on 101 postmenopausal women in a university-affiliated nursing home to investigate if there is an association between osteoporosis or osteopenia and AVD. Bone mineral density (BMD) was measured by DEXA scan obtained from a computerized radiology database. Low BMD was defined as > or =1.5 standard deviations below the mean of a cohort of young women. AVD was diagnosed if documented coronary artery disease, cerebrovascular disease, or peripheral arterial disease was present. The mean age and prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia were not significantly different between 51 women with osteoporosis or osteopenia and 50 women with normal BMD. AVD was present in 31 of 51 women (51%) with osteoporosis or osteopenia and in 19 of 50 women (38%) with a normal BMD (p<0.025).

Underuse of procedures for diagnosing osteoporosis and of therapies for osteoporosis in older nursing home residents.

OBJECTIVE: To investigate the prevalence of osteoporosis, the prevalence of utilization of bone mineral density (BMD) measurements for diagnosis of osteoporosis, and prevalence of use of calcium and vitamin D supplements and other antiresorptive therapies for treatment of osteoporosis in postmenopausal women in an academic nursing home. METHODS: The charts of all women aged 56 years and older residing in an academic nursing home were analyzed by one of the authors for the prevalence of osteoporosis, the prevalence of use of BMD measurements to diagnose osteoporosis, and the prevalence of use of calcium and vitamin D supplements and other antiresorptive therapies for treatment of osteoporosis. RESULTS: Of 136 postmenopausal women, mean age 79 +/- 10 years, 66 (49%) had measurements of BMD. Of these 66 women, 31 (47%) had osteoporosis, 21 (32%) had osteopenia, and 14 (21%) had normal BMD. Elemental calcium carbonate 1500 mg daily was prescribed to 17 of 31 women (55%) with osteoporosis, to 12 of 21 women (57%) with osteopenia, to 2 of 14 women (14%) with normal BMD, and to 27 of 70 women (39%) with no BMD obtained. Any dose of calcium was prescribed to 78 of 136 elderly women (58%). Vitamin D supplements were prescribed to 13 of 31 women (42%) with osteoporosis, to 9 of 21 women (43%) with osteopenia, to 2 of 14 women (14%) with normal BMD, and to 20 of 70 women (29%) with no BMD obtained. Vitamin D supplements were prescribed to 44 of 136 elderly women (32%). Biphosphonates were prescribed to 19 of 31 women (61%) with osteoporosis. Of 20 women on medications that increased the risk of osteoporosis, 6 (30%) had BMD measured. Nine of these 20 women (45%) were on calcium supplements. CONCLUSIONS: Older postmenopausal women in an academic nursing home have a high prevalence of osteoporosis and osteopenia, a low prevalence of measurement of BMD, and underuse of calcium, vitamin D supplements, and other antiresorptive therapies for treatment of osteoporosis.