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The intention of the current article is to review the epidemiology with related socioeconomic costs, pathophysiology, and treatment options for diaphyseal long bone delayed unions and nonunions. Diaphyseal nonunions in the tibia and in the femur are estimated to occur 4.6-8% after modern intramedullary nailing of closed fractures with an even much higher risk in open fractures. There is a high socioeconomic burden for long bone nonunions mainly driven by indirect costs, such as productivity losses due to long treatment duration. The classic classification of Weber and Cech of the 1970s is based on the underlying biological aspect of the nonunion differentiating between "vital" (hypertrophic) and "avital" (hypo-/atrophic) nonunions, and can still be considered to represent the basis for basic evaluation of nonunions. The "diamond concept" units biomechanical and biological aspects and provides the pre-requisites for successful bone healing in nonunions. For humeral diaphyseal shaft nonunions, excellent results for augmentation plating were reported. In atrophic humeral shaft nonunions, compression plating with stimulation of bone healing by bone grafting or BMPs seem to be the best option. For femoral and tibial diaphyseal shaft fractures, dynamization of the nail is an atraumatic, effective, and cheap surgical possibility to achieve bony consolidation, particularly in delayed nonunions before 24 weeks after initial surgery. In established hypertrophic nonunions in the tibia and femur, biomechanical stability should be addressed by augmentation plating or exchange nailing. Hypotrophic or atrophic nonunions require additional biological stimulation of bone healing for augmentation plating.

Background Future projections for both TKA and THA in the United States and other countries forecast a further increase of already high numbers of joint replacements. The consensus is that in industrialized countries, this increase is driven by demographic changes with more elderly people being less willing to accept activity limitations. Unlike the United States, Germany and many other countries face a population decline driven by low fertility rates, longer life expectancy, and immigration rates that cannot compensate for population aging. Many developing countries are likely to follow that example in the short or medium term amid global aging. Due to growing healthcare expenditures in a declining and aging population with a smaller available work force, reliable predictions of procedure volume by age groups are requisite for health and fiscal policy makers to maintain high standards in arthroplasty for the future population. Questions/purposes (1) By how much is the usage of primary TKA and THA in Germany expected to increase from 2016 through 2040? (2) How is arthroplasty usage in Germany expected to vary as a function of patient age during this time span? Methods The annual number of primary TKAs and THAs were calculated based on population projections and estimates of future healthcare expenditures as a percent of the gross domestic product (GDP) in Germany. For this purpose, a Poisson regression analysis using age, gender, state, healthcare expenditure, and calendar year as covariates was performed. The dependent variable was the historical number of primary TKAs and THAs performed as compiled by the German federal office of statistics for the years 2005 through 2016. Results Through 2040, the incidence rate for both TKA and THA will continue to increase annually. For TKA, the incidence rate is expected to increase from 245 TKAs per 100,000 inhabitants to 379 (297-484) (55%, 95% CI 21 to 98). The incidence rate of THAs is anticipated to increase from 338 to 437 (357-535) per 100,000 inhabitants (29% [95% CI 6 to 58]) between 2016 and 2040. The total number of TKAs is expected to increase by 45% (95% CI 14 to 8), from 168,772 procedures in 2016 to 244,714 (95% CI 191,920 to 312,551) in 2040. During the same period, the number of primary THAs is expected to increase by 23% (95% CI 0 to 50), from 229,726 to 282,034 (95% CI 230,473 to 345,228). Through 2040, the greatest increase in TKAs is predicted to occur in patients aged 40 to 69 years (40- to 49-year-old patients: 269% (95% CI 179 to 390); 50- to 59-year-old patients: 94% (95% CI 48 to 141); 60- to 69-year-old patients: 43% (95% CI 13 to 82). The largest increase in THAs is expected in the elderly (80- to 89-year-old patients (71% [95% CI 40 to 110]). Conclusions Although the total number of TKAs and THAs is projected to increase in Germany between now and 2040, the increase will be smaller than that previously forecast for the United States, due in large part to the German population decreasing over that time, while the American population increases. Much of the projected increase in Germany will be from the use of TKA in younger patients and from the use of THA in elderly patients. Knowledge of these trends may help planning by surgeons, hospitals, stakeholders, and policy makers in countries similar to Germany, where high incidence rates of arthroplasty, aging populations, and overall decreasing populations are present. Level of Evidence Level III, economic and decision analysis.

The Bayer-Activities of Daily Living Scale (B-ADL) is a 25-item, informant-rated questionnaire which was developed as a brief and internationally applicable instrument for assessing functional disabilities. The scale’s target group are elderly patients suffering from mild to moderate dementia or cognitive impairment. To investigate the reliability and validity of different language versions, the B-ADL was administered in the UK, Germany, and Spain to a total of 1,433 subjects with a wide range of cognitive decline. The results from the three country samples were very similar, with internal consistency being above 0.98 (Cronbach alpha). A factor analysis revealed that a one-factor solution accounted for most of the variance. The B-ADL total score significantly increased between adjacent Global Deterioration Scale (GDS) stages 1 to 5. A second factor analysis entering additional variables (GDS stage, Mini-Mental State Examination or MMSE subscores, age, years of education, gender, and country) revealed that all B-ADL items loaded on the same factor, ‘dementia severity’, and that they were not related to age, education, gender, or country. In the identification of subjects with clinically manifest dementia symptoms (GDS stages 4 and 5), the B-ADL proved to be as efficient as the MMSE in the UK and German samples and superior to the MMSE in the Spanish sample.

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BackgroundHypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung that matches blood perfusion to alveolar ventilation to optimize gas exchange. Recently we have demonstrated that acute but not sustained HPV is critically dependent on the classical transient receptor potential 6 (TRPC6) channel. However, the mechanism of TRPC6 activation during acute HPV remains elusive. We hypothesize that a diacylglycerol (DAG)-dependent activation of TRPC6 regulates acute HPV.MethodsWe investigated the effect of the DAG analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) on normoxic vascular tone in isolated perfused and ventilated mouse lungs from TRPC6-deficient and wild-type mice. Moreover, the effects of OAG, the DAG kinase inhibitor R59949 and the phospholipase C inhibitor U73122 on the strength of HPV were investigated compared to those on non-hypoxia-induced vasoconstriction elicited by the thromboxane mimeticum U46619.ResultsOAG increased normoxic vascular tone in lungs from wild-type mice, but not in lungs from TRPC6-deficient mice. Under conditions of repetitive hypoxic ventilation, OAG as well as R59949 dose-dependently attenuated the strength of acute HPV whereas U46619-induced vasoconstrictions were not reduced. Like OAG, R59949 mimicked HPV, since it induced a dose-dependent vasoconstriction during normoxic ventilation. In contrast, U73122, a blocker of DAG synthesis, inhibited acute HPV whereas U73343, the inactive form of U73122, had no effect on HPV.ConclusionThese findings support the conclusion that the TRPC6-dependency of acute HPV is induced via DAG.

It is demonstrated that neither deletion of HO-2 nor BK channels affect acute, sustained, and chronic vascular responses to alveolar hypoxia in the lung.