Andrea Berghold

Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review

According to current guidelines, pulmonary arterial hypertension (PAH) is diagnosed when mean pulmonary arterial pressure (P̄pa) exceeds 25 mmHg at rest or 30 mmHg during exercise. Issues that remain unclear are the classification of P̄pa values <25mmHg and whether P̄pa >30 mmHg during exercise is always pathological. We performed a comprehensive literature review and analysed all accessible data obtained by right heart catheter studies from healthy individuals to determine normal P̄pa at rest and during exercise. Data on 1,187 individuals from 47 studies in 13 countries were included. Data were stratified for sex, age, geographical origin, body position and exercise level. P̄pa at rest was 14.0±3.3 mmHg and this value was independent of sex and ethnicity. Resting P̄pa was slightly influenced by posture (supine 14.0±3.3 mmHg, upright 13.6±3.1 mmHg) and age (<30 yrs: 12.8± 3.1mmHg; 30–50 yrs: 12.9±3.0 mmHg; ≥50 yrs: 14.7±4.0 mmHg). P̄pa during exercise was dependent on exercise level and age. During mild exercise, P̄pa was 19.4±4.8 mmHg in subjects aged <50 yrs compared with 29.4±8.4 mmHg in subjects ≥50 yrs (p<0.001). In conclusion, while P̄pa at rest is virtually independent of age and rarely exceeds 20 mmHg, exercise P̄pa is age-related and frequently exceeds 30 mmHg, especially in elderly individuals, which makes it difficult to define normal P̄pa values during exercise.

Patterns of cortical activation during planning of voluntary movement

The influence of planning of self-paced voluntary finger movements on alpha band components was studied in 6 volunteers. Brain potentials from 29 electrodes, referred to the right ear, were recorded 4 sec before and 2 sec after movement onset. These data were transformed to obtain the laplacian operator, which was done by computing the local average reference. The event-related desynchronization (ERD) of upper alpha components was then calculated in each record at intervals of 250 msec and topographically displayed in the form of serial ERD maps. A first significant ERD (P less than 0.01, sign test) was found 1.75 sec +/- 0.61 before the movement, most prominent over the contralateral sensorimotor area and over midfrontal areas (the latter can probably be interpreted as an activation of the supplementary motor area). From these data we can conclude that the side of movement is predetermined more than 1 sec before movement onset.

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis

AimsWe compared the effects of continuous subcutaneous insulin infusion (CSII) with those of multiple daily insulin (MDI) injections on glycaemic control, risk of hypoglycaemic episodes, insulin requirements and adverse events in type 1 and type 2 diabetes mellitus.MethodsThe electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for randomised controlled trials up to March 2007. A systematic review and meta-analysis were performed.ResultsOverall, 22 studies were included (17 on type 1 diabetes mellitus, two on type 2 diabetes mellitus, three on children). With regard to adults with type 1 diabetes mellitus, our meta-analysis found a between-treatment difference of −0.4% HbA1c (six studies) in favour of CSII therapy. Available median rates of mild or overall hypoglycaemic events were comparable between the different interventions (1.9 [0.9–3.1] [CSII] vs 1.7 [1.1–3.3] [MDI] events per patient per week). Total daily insulin requirements were lower with CSII than with MDI therapy. In patients with type 2 diabetes mellitus, CSII and MDI treatment showed no statistically significant difference for HbA1c. The incidence of mild hypoglycaemic events was comparable between the treatment groups. In adolescents with type 1 diabetes mellitus, glycated haemoglobin and insulin requirements were significantly lower in the CSII groups; no data were available on hypoglycaemic events. The only study performed in younger children did not provide enough data for conclusive inferences. No overall conclusions were possible for severe hypoglycaemia and adverse events for any of the different patient groups due to rareness of such events, different definitions and insufficient reporting.Conclusions/interpretationCSII therapy in adults and adolescents with type 1 diabetes mellitus resulted in a greater reduction of glycated haemoglobin, in adult patients without a higher rate of hypoglycaemia. No beneficial effect of CSII therapy could be detected for patients with type 2 diabetes mellitus.

Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.

IMPORTANCE Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. OBJECTIVE To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. DESIGN, SETTING, AND PARTICIPANTS A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243). INTERVENTIONS Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months. MAIN OUTCOMES AND MEASURES The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis. RESULTS A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01130181.

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR‐based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis.

Transjugular Intrahepatic Portosystemic Shunt Creation with the Viatorr Expanded Polytetrafluoroethylene–Covered Stent-Graft

PURPOSE To evaluate the midterm clinical results and patency of transjugular portosystemic shunts (TIPS) created with a commercially available expanded polytetrafluoroethylene (ePTFE)-covered stent-graft based on angiographic and ultrasonographic (US) criteria in a series of 71 patients. MATERIALS AND METHODS Seventy-one patients (61 men, 10 women; mean age, 58.6 years, range, 25-78 years) were included in this series, which was performed in two centers. Indications for TIPS creation were refractory ascites (n = 44) and recurrent esophageal bleeding (n = 27). Ten patients had Child-Pugh class A liver cirrhosis, 43 had class B disease, and 18 had class C disease. Underlying liver diseases were alcoholic cirrhosis (n = 58), cirrhosis resulting from hepatitis (n = 9), cryptogenic cirrhosis (n = 3), and Budd-Chiari syndrome (n = 1). TIPS were created with commercially available ePTFE-covered stent-grafts in all patients. The diameters of the stent-grafts were 10 mm in 58 patients and 8 mm in the remaining 13 patients. Follow-up included clinical examination and color-coded US after 5 days, 1, 3, and 6 months, and every 6 months thereafter. Shunt angiograms were obtained every 6 months. Median follow-up was 16.3 months (range, 3.8-26.6 months). RESULTS TIPS creation was successful in all patients without complications, and effective portal decompression was observed with a reduction of the mean portal gradient from 19 mm Hg to 6 mm Hg before and after TIPS creation. Four shunt occlusions were observed after 5 days, 2 months, 3 months, and 6 months. Shunt stenosis was observed in three patients at the hepatic vein, which was not fully covered by the stent-graft, after 6 months (n = 2) and 12 months, and at the portal side after 1 month in a patient who initially had portal vein thrombosis. The repeat intervention rate was 11.3%. The primary patency rates were 87.4% (95% CI, 77.7%-97.1%) after 6 months and 80.8% (95% CI, 68.2%-93.4%) after 12 months. The rate of de novo or deteriorated hepatic encephalopathy was 31%. The recurrent bleeding rate was 3.7% (one of 27), and ascites improved or resolved in 64% of patients after 1 month. CONCLUSION TIPS patency can be significantly increased if the ePTFE-covered stent-graft is used for shunt creation. The increased shunt patency contributes to low repeat intervention and recurrent bleeding rates. The rate of hepatic encephalopathy is within the range of previously reported rates.

Calcinosis cutis: Part I. Diagnostic pathway

Calcinosis cutis is characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue. The syndrome is separated into five subtypes: dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification, and calciphylaxis. Dystrophic calcification appears as a result of local tissue damage with normal calcium and phosphate levels in serum. Metastatic calcification is characterized by an abnormal calcium and/or phosphate metabolism, leading to the precipitation of calcium in cutaneous and subcutaneous tissue. Idiopathic calcification occurs without any underlying tissue damage or metabolic disorder. Skin calcification in iatrogenic calcinosis cutis is a side effect of therapy. Calciphylaxis presents with small vessel calcification mainly affecting blood vessels of the dermis or subcutaneous fat. Disturbances in calcium and phosphate metabolism and hyperparathyroidism can be observed.

Pulmonary vascular resistances during exercise in normal subjects: a systematic review

The physiological range of pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR), and the impact of exercise, age and posture have been a matter of debate for many years. We performed a systematic literature review including all right heart catheterisation data where individual PVR and TPR of healthy subjects both at rest and exercise were available. Data were stratified according to age, exercise level and posture. Supine resting PVR in subjects aged <24 yrs, 24–50 yrs, 51–69 yrs and ≥70 yrs was 61±23, 69±28, 86±15 and 90±39 dyn·s·cm−5, respectively. Corresponding TPR was 165±50, 164±46, 226±64 and 223±45 dyn·s·cm−5, respectively. During moderate exercise in subjects aged ≤50 yrs, an 85% increase in cardiac output was associated with a 25% decrease in TPR (p<0.0001) and a 12% decrease in PVR (p<0.01). At 51–69 yrs of age there was no significant decrease in TPR and PVR. In individuals aged ≥70 yrs TPR even increased by 17% (p=0.01), while PVR did not change significantly. At higher exercise levels, TPR decreased in all age groups. In the upright position, based on a limited number of data, resting TPR and PVR were higher than in the supine position and decreased more prominently during exercise, suggesting the release of resting pulmonary vasoconstriction. These data may form a basis to define normal PVR at rest and exercise.

Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems.

Study Design. Retrospective study. Objective. This study analyzed the predictive value of the scoring systems of Bauer, Bauer modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos as well as the parameters included in these systems. Summary of Background Data. Metastases of the spinal column are a common manifestation of advanced cancer. Severe pain, pathologic fracture, and neurologic deficit due to spinal metastases need adequate treatment. Besides oncologic aspects and quality of life, treatment decisions should also include the survival prognosis. Methods. Two hundred fifty-four patients with confirmed spinal metastases were investigated retrospectively (treatment 1998–2006; 62 underwent surgery and 192 had conservative treatment only). Factors related to survival, such as primary tumor, general condition (Karnofsky Performance Status Scale), neurologic deficit, number of spinal and extraspinal bone metastases, visceral metastases, and pathologic fracture, were analyzed. The survival period was calculated from date of diagnosis of the spinal metastases to date of death or last follow-up (minimum follow-up: 12 months). For statistical analysis, univariate and stepwise multivariate Cox regression analyses were performed. Results. Median overall survival for all patients was 10.6 months. The following factors showed significant influence on survival in multivariate analysis: primary tumor (P < 0.0001), status of visceral metastases (P < 0.0001), and systemic therapy (P < 0.0001). Using the recommended group assignment for each system, only Bauer and Bauer modified showed significant results for the distinction between good, moderate, and poor prognosis. The other systems failed to distinguish significantly between good and moderate prognosis. The hazard ratio of the absolute score of all analyzed systems was, however, statistically significant, with a better score leading to lower risk of death. Conclusion. According to this analysis, the Bauer and the Bauer modified scores are the most reliable systems for predicting survival. Since the Bauer modified score furthermore consists of only four positive prognostic factors, we emphasize its impact and simplicity.

Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma

OBJECTIVE To investigate the incidence and clinical findings of radiation retinopathy after single-fraction high-dose gamma knife radiosurgery for choroidal melanoma. DESIGN Retrospective noncomparative interventional case series. PARTICIPANTS Thirty-two patients with choroidal melanoma. METHODS Review of charts, color fundus photographs, and fluorescein angiograms of 32 choroidal melanoma patients after radiosurgery. All patients were treated with the Leksell gamma knife in one fraction with a marginal dose between 40 and 80 Gy (median, 50 Gy) and were followed for at least 24 months (or until enucleation because of complications secondary to radiation). MAIN OUTCOME MEASURES Any clinical feature of radiation retinopathy and neovascular glaucoma. RESULTS During a mean follow-up of 38 months (range, 6-81 months) we found radiation retinopathy in 84% of our patients. The most common findings in these patients were intraretinal hemorrhages with an incidence of 70%, macular edema and capillary nonperfusion in 63%, and hard exudates in 52% of the patients. Less common were microaneurysms in 30% and retinal neovascularization in 22%. The time of onset of the various radiation-associated retinal findings ranged between 1 and 22 months. Forty-seven percent of all patients developed neovascular glaucoma. In our study there was no correlation between radiation dosage applied and clinical findings. CONCLUSIONS Single-fraction high-dose Leksell gamma knife radiosurgery of choroidal melanomas with a median marginal dose of 50 Gy is highly associated with early radiation retinopathy and with neovascular glaucoma.