Diabetes and osteoporosis

Care of patients with diabetes should include assessment of bone health. The extension of the average life expectancy of people with diabetes, which has accompanied improvements in medical care, has also increased the significance of osteoporosis. In addition to the usual causes of osteoporosis associated with aging, bone health is also compromised by diabetes. Studies on bone involvement in patients with diabetes mellitus have generated conflicting results, largely because of the pathogenetic complexity of the condition. It is now clear that patients with type 1 diabetes have lower bone mineral density (BMD) and a higher risk of fractures. Evidence is emerging that patients with type 2 diabetes who have complications are also at increased risk of certain types of osteoporotic fractures, despite having a higher BMD when compared to patients with type 1 diabetes. Although many factors, including number and type of falls, visual impairment, neuropathy, and reduced muscle strength, influence the probability of fractures, the most significant factor seems to be the strength of the bone itself. Thus, sarcopenia, a reduction in muscle mass and muscle strength, is considered one of the main determinants of bone fragility. The aim of this review is to examine the occurrence of osteoporosis in type 1 and type 2 diabetes.     

Acute epiglottis in adults

Acute epiglottitis can be a serious life-threatening disease because of its potential for sudden upper airway obstruction. It is a well-recognised entity in children but it is uncommon in adults and therefore is often misdiagnosed. In this retrospective study we present twelve cases of acute epiglottitis in adults. The diagnosis was made by visualisation of the epiglottis using fibreoptic laryngoscopy. The illness was managed using a standardised management protocol (see Appendix). The most frequent symptoms were odynophagia (100%), inability to swallow secretions (83%), sore throat (67%), dyspnoea (58%) and hoarseness (50%). Body temperature was elevated (>37.2 degrees C) in 75% and 50% of the patients had tachycardia (>100 bpm). The supposedly typical sign of stridor was found in only 42% of the cases. A routine oropharyngeal examination does not exclude epiglottitis, 44% of our patients had a normal oropharynx and the diagnosis could only be made following fibreoptic laryngoscopy. Nasotracheal intubation was necessary in four patients. A 40-year-old man with sore throat, hoarseness, cough and odynophagia was initially seen by a physician. With the suspected diagnosis of an infection - induced exacerbation of bronchial asthma, he was treated with antibiotics, paracetamol und corticosteroids. On admission six hours later the patient was in coma. The diagnosis was not made until conventional oral endotracheal intubation (without a tracheotomy set placed at the bedside) was attempted. Unfortunately the intubation failed and the patient died. Medical management of epiglottitis in adults includes an antibiotics, NSAIDs and possibly inhalation with adrenaline. The maintenance of an adequate open airway is the main concern in adults as well as in children. Although most adults have no signs of airway obstruction, the clinical threshold for insertion of an airway should remain low, as it is the only way of preventing death. A high index of suspicion is needed to recognise this rare disease correctly and patients must be admitted to a hospital with intensive care facilities, where the diagnosis can be confirmed and intubation performed if necessary and thus reduce the mortality rate.     

Transplantation of peripheral blood progenitor cells from HLA-identical sibling donors

Transplantation of peripheral blood progenitor cells (PBPCs) has largely replaced autologous bone marrow transplantation. The same might occur in the allogeneic setting if the favourable initial experience with allogeneic PBPCT is confirmed. We analysed all primary transplants utilizing unmodified PBPC from HLA-identical sibling donors reported to the European Group for Blood and Marrow Transplantation (EBMT) for 1994. 59 patients with a median age of 39 years received myeloablative therapy for acute myelogenous leukaemia (23 patients), acute lymphoblastic leukaemia (13), chronic myelogenous leukaemia (nine), lymphoma (seven), or other diagnoses (seven) mostly of advanced stages followed by transplantation of allogeneic PBPC. Three patients died soon after grafting, the others showed prompt haemopoietic recovery with median times to recover an absolute neutrophil count (ANC) above 0.5 and 1.0×10⁹/l of 15 (range 9–27) and 17 d (range 10–28) respectively. Time to platelet recovery above 20 or 50×10⁹/l was 16 (range 9–76) and 18 d (range 12–100) respectively. 27 patients (46%) developed no or mild acute graft-versus-host disease (GVHD). The incidence of moderate (grade II) disease was 27%; 24% of the patients developed severe acute GVHD (grades III or IV). 55% of patients who were alive 90 d after transplantation developed chronic GVHD, the probability to develop extensive chronic GVHD was 32% (95% confidence interval 22–42) with a median follow-up of 14 months. Overall and event-free survival (EFS) at 1 year were 54% (CI 48–60) and 50% (CI 43–57), respectively, the relapse incidence was 23% (CI 17–29). EFS was 67% (CI 55–79) in patients transplanted for acute leukaemias in first complete remission, chronic myelogenous leukaemia in first chronic phase, or severe aplastic anaemia. Transplantation of allogeneic PBPC resulted in prompt and durable engraftment. The incidence and severity of acute and chronic GVHD seemed comparable to that observed after allogeneic BMT. Overall and event-free survival in this cohort of patients, most of whom suffered from advanced leukaemia or lymphoma, is encouraging, suggesting that the high numbers of T lymphocytes and/or natural killer cells contained in a typical PBPC collection product exert a vigorous graft-versus-leukaemia effect. Further evaluation of allogeneic PBPCT is highly desirable.     

Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia

Bone marrow transplantation (BMT) and immunosuppression (IS) have improved the prognosis of aplastic anemia; both treatments have specific advantages and drawbacks but similar survival rates. Analysis of additional endpoints may help in treatment decisions. In a single-center study, patients with aplastic anemia treated with IS (n=155) or BMT (n=52) were compared for survival, event-free survival, and quality-adjusted time without symptoms and toxicity (Q-TWiST). Probability of overall and event-free survival at 15 years was similar among both groups (BMT 51±15% and 25±14%, IS 53±10% and 27±8%), with more early deaths in the transplant group and more late deaths in the IS group. There were differences in terms of mean duration of seven analyzed health states: time with symptoms from treatment-related toxicity (IS 0.36 years, BMT 0.27), transfusion dependency (IS 0.66 years, BMT 0.1 years), partial remission (IS 3.27 years, BMT 1.42), and secondary clonal disorder (IS 0.68 years, BMT 0.04) was significantly longer for IS compared to BMT (p0.001). Patients treated with BMT spent more time with extensive chronic graft-versus-host disease (GvHD) (IS 0 years, BMT 0.96, p<0.023) and in CR without drugs (IS 1.22 years, BMT 2.43, p=0.056). In conclusion, survival, event-free survival, and Q-TWiST are similar. BMT-treated patients had longer periods free from symptoms, while IS-treated patients needed closer medical care, transfusion support, and medications.     

Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia

In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond ( n  = 25) or relapse ( n  = 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P  > 0.2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses ( P  > 0.2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13 d; P  = 0.008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 ± 8% at 10 years. The probability of developing a late clonal disorder was 53 ± 10% after multiple, as compared to 34 ± 7% after single exposure ( P  = 0.15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.     

Colonic J-Pouch vs. Coloplasty Following Resection of Distal Rectal Cancer

PURPOSE: In terms of functional outcome, there is evidence of the superiority of the colonic J-pouch over a straight coloanal anastomosis. Even though the colonic J-pouch was created to restore a neorectal reservoir, manometric data show that the volume of a short colonic J-pouch does not differ from a straight coloanal anastomosis. We speculate that the advantage of the colonic J-pouch is not in creating a larger neorectal reservoir, but rather related to decreased motility. Maurer and Zgraggen recently described a new colonic pouch design, performing a transverse coloplasty pouch. The purpose of this pilot study was to compare the feasibility and functional outcome of the 5-cm colonic J-pouch vs. the coloplasty pouch. METHODS: From February 2000 to June 2001, we randomized 40 consecutive patients with distal rectal cancer (<12 cm from the anal verge) into the J-pouch or coloplasty group. A low rectal resection and coloanal anastomosis was performed in all patients. Functional data were collected by a standardized questionnaire and anorectal manometry, preoperatively and six months postoperatively. Primary end points of the study were potentially differences of both groups regarding technical feasibility, stool frequency, and anorectal manometry. RESULTS: The construction of a coloplasty pouch was feasible in all cases of the coloplasty group, but not in 5 of 20 (25 percent) patients of the J-pouch group, because of colonic adipose tissue. Six months after operation or stoma closure, respectively, stool frequency was 2.75 ± 1 per day in the J-pouch group and 2 ± 2 per day in the coloplasty group. There was no significant difference in resting and squeeze pressure and neorectal volume between both groups, but an increased neorectal sensitivity in the coloplasty group. CONCLUSION: We found similar functional results in the coloplasty group compared to the J-pouch group. The neorectal sensitivity was increased in the coloplasty group. Therefore, the colonic coloplasty seems to be an attractive pouch design because of its feasibility, simplicity, and effectiveness.     

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.     

Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a Global Observational Study

Fifty-five years after publication of the first hematopoietic stem cell transplantation this technique has become an accepted treatment option for defined hematologic and non-hematologic disorders. There is considerable interest in understanding differences in its use and trends on a global level and the macro-economic factors associated with these differences. Data on the numbers of hematopoietic stem cell transplants performed in the 3-year period 2006–2008 were obtained from Worldwide Network for Blood and Marrow Transplantation member registries and from transplant centers in countries without registries. Population and macro-economic data were collected from the World Bank and from the International Monetary Fund. Transplant rates were analyzed by indication, donor type, country, and World Health Organization regional offices areas and related to selected health care indicators using single and multiple linear regression analyses. Data from a total of 146,808 patients were reported by 1,411 teams from 72 countries over five continents. The annual number of transplants increased worldwide with the highest relative increase in the Asia Pacific region. Transplant rates increased preferentially in high income countries (P=0.02), not in low or medium income countries. Allogeneic transplants increased for myelodysplasia, chronic lymphocytic leukemia, acute leukemias, and non-malignant diseases but decreased for chronic myelogenous leukemia. Autologous transplants increased for autoimmune and lymphoproliferative diseases but decreased for leukemias and solid tumors. Transplant rates (P<0.01), donor type (P<0.01) aand disease indications (P<0.01) differed significantly between countries and regions. Transplant rates were associated with Gross National Income/capita (P<0.01) but showed a wide variation of explanatory content by donor type, disease indication and World Health Organization region. Hematopoietic stem cell transplantation activity is increasing worldwide. The preferential increase in high income countries, the widening gap between low and high income countries and the significant regional differences suggest that different strategies are required in individual countries to foster hematopoietic stem cell transplantation as an efficient and cost-effective treatment modality.