Changes in Skeletal Microstructure Through Four Continuous Years of rhPTH(1–84) Therapy in Hypoparathyroidism

Bone remodeling is reduced in hypoparathyroidism, resulting in increased areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and abnormal skeletal indices by transiliac bone biopsy. We have now studied skeletal microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT) through 4 years of treatment with recombinant human PTH(1–84) (rhPTH[1–84]) in 33 patients with hypoparathyroidism (19 with postsurgical disease, 14 idiopathic). We calculated Z-scores for our cohort compared with previously published normative values. We report results at baseline and 1, 2, and 4 years of continuous therapy with rhPTH(1–84). The majority of patients (62%) took rhPTH(1–84) 100 μg every other day for the majority of the 4 years. At 48 months, areal bone density increased at the lumbar spine (+4.9% ± 0.9%) and femoral neck (+2.4% ± 0.9%), with declines at the total hip (−2.3% ± 0.8%) and ultradistal radius (−2.1% ± 0.7%) (p < .05 for all). By HR-pQCT, at the radius site, very similar to the ultradistal DXA site, total volumetric BMD declined from baseline but remained above normative values at 48 months (Z-score + 0.56). Cortical volumetric BMD was lower than normative controls at baseline at the radius and tibia (Z-scores −1.28 and − 1.69, respectively) and further declined at 48 months (−2.13 and − 2.56, respectively). Cortical porosity was higher than normative controls at baseline at the tibia (Z-score + 0.72) and increased through 48 months of therapy at both sites (Z-scores +1.80 and + 1.40, respectively). Failure load declined from baseline at both the radius and tibia, although remained higher than normative controls at 48 months (Z-scores +1.71 and + 1.17, respectively). This is the first report of noninvasive high-resolution imaging in a cohort of hypoparathyroid patients treated with any PTH therapy for this length of time. The results give insights into the effects of long-term rhPTH(1–84) in hypoparathyroidism. © 2020 American Society for Bone and Mineral Research.     

Long sleep duration and cardiovascular disease: Associations with arterial stiffness and blood pressure variability

Although short and long sleep duration are both risk factors of cardiovascular disease (CVD), the recent meta‐analyses have been shown that long sleep duration was closely associated with CVD mortality. While the specific mechanism underlying the association between long sleep duration and CVD remains unclear, long sleep duration was shown to be associated with arterial stiffness and blood pressure variability (BPV) in many Asian populations. This review article will focus on the pathophysiology of long sleep duration, arterial stiffness, BPV and their effects on CVD. To set the stage for this review, we first summarize the current insights for the relationship between long sleep duration and CVD in relation to arterial stiffness and BPV.     

Hypertension and erectile dysfunction: The role of endovascular therapy in Asia

The prevalence of erectile dysfunction (ED) is above 40% in both Asian and non‐Asian male populations after the age of 40 years. The prevalence of ED among hypertensive patients is approximately double than that in normotensive population. Pelvic arterial insufficiency is the predominant cause of ED in men aged over 50 years. Stenosis in any segment of the iliac–pudendal–penile arterial system, which is considered an erectile‐related arterial axis, could lead to ED. Pharmacotherapy with lifestyle modification is effective in alleviating sexual dysfunction, yet a substantial number of patients still develop ED. Given the established applicability of angioplasty for the entire iliac–pudendal–penile arterial system, penile duplex ultrasound, and pelvic computed tomography angiography could be considered as the routine screening tools in ED patients with poor response to phosphodiesterase‐5 inhibitors. Endovascular therapy for pelvic arterial insufficiency‐related ED has been shown to be a safe and effective treatment option in patients who have anatomically suitable vessels and functionally significant stenoses. Clinical improvement was achieved in over 60% of patients at one year following pelvic angioplasty in the PERFECT registry from Taiwan. A 30%‐40% restenosis rate in distal internal pudendal and penile arteries remains a hurdle. Angioplasty for pelvic arterial occlusive disease could be considered as a viable approach to arteriogenic ED.     

Use of arterial transfer functions for the derivation of aortic waveform characteristics

OBJECTIVE: To investigate the utility and accuracy of radial-aortic arterial transfer functions for the derivation of central blood pressure waveforms.DESIGN Prospective measurement of central and peripheral waveforms in patients undergoing coronary angiography or percutaneous coronary intervention. METHODS: Simultaneous invasive central aortic and non-invasive radial pressure waveforms were recorded in 78 subjects (61 male : 17 female). Data were applied to a single-input/single-output model for the calculation of a transfer function (TF). Individual TFs were derived by two methods and ensemble averaged TFs obtained for the group. Reverse transformation was performed using each averaged TF applied to the radial data of each subject. RESULTS: There was close linear correlation between measured aortic parameters and both radial and TF-derived aortic systolic and diastolic pressures (P < 0.001) and most other waveform parameters. However, despite small mean differences between measured and most TF-derived aortic parameters (systolic pressure 0.8-2.9 mmHg, augmentation index 4.3-5.6%), individual scatter was marked, with 95% limits of agreement of +/- 14.6 mmHg (systolic pressure) and +/- 24.4% [augmentation index (AI)]. Indeed, scatter for AI was so marked that measured and derived values were not statistically significantly correlated. CONCLUSIONS: Transfer functions may be valid for the derivation of some central aortic waveform characteristics. However, in providing neither improved reproducibility nor data on parameters not obtainable from the radial waveform, transfer function techniques may offer no additional clinical benefit. The absence of correlation between measured and TF-derived aortic AI and wide limits of agreement of other parameters should be considered if this technique is utilized in clinical practice.     

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.