Hypothyroidism and levothyroxine therapy following bariatric surgery: a systematic review,meta-analysis,network meta-analysis,and meta-regression

BackgroundMany health benefits of bariatric surgery are known and well-studied, but there is scarce data on the benefits of bariatric surgery on the thyroid function.ObjectiveWe aimed to make a meta-analysis regarding the impact of bariatric surgery on thyroid-stimulating hormone (TSH) levels, levothyroxine dose, and the status of subclinical hypothyroidism.SettingSystematic review and meta-analysis.MethodsPubMed, EMBASE, and Cochrane Library were searched up to December 2020 for relevant clinical studies. Random-effects model was used to pool results. Network meta-analysis was performed, incorporating direct and indirect comparisons among different types of bariatric surgery. Meta-regression analysis was performed to evaluate the impact of moderator variables on TSH levels and required levothyroxine dose after surgery. We followed the PRISMA guidelines for data selection and extraction. PROSPERO registry number: CRD42018105739.ResultsA total of 28 studies involving 1284 patients were included. There was a statistically significant decrease in TSH levels after bariatric surgery (mean difference = ?1.66 mU/L, 95%CI [?2.29, ?1.03], P < .0001). In meta-regression analysis, we found that the following moderator variables: length of follow-up, mean age, baseline TSH, and preoperative thyroid function, could explain 1%, 43%, 68%, and 88% of the between-study variance, respectively. Furthermore, subclinical hypothyroidism was completely resolved in 87% of patients following bariatric surgery. In addition, there was a statistically significant decrease of levothyroxine dose in frank hypothyroid patients following bariatric surgery (mean difference = ?13.20 mcg/d, 95%CI [?19.69, ?6.71]). In network meta-analysis, we found that discontinuing or decreasing levothyroxine dose was significant following Roux-en-Y gastric bypass, 1 anastomosis gastric bypass, and sleeve gastrectomy, (OR = 31.02, 95%CI [10.34, 93.08]), (OR = 41.73, 95%CI [2.04, 854.69]), (OR = 104.03, 95%CI [35.79, 302.38]), respectively.ConclusionsBased on our meta-analysis, bariatric surgery is associated with the resolution of subclinical hypothyroidism, a decrease in TSH levels, and a decrease in levothyroxine dose.     

Intracytoplasmic injection of fresh and cryopreserved testicular spermatozoa in patients with nonobstructive azoospermia—a comparative study

Objective: To compare the outcome of intracytoplasmic sperm injection (ICSI) with fresh and frozen-thawed testicular spermatozoa in patients with nonobstructive azoospermia.Design: Retrospective analysis of consecutive ICSI cycles.Setting: In Vitro Fertilization Unit, Assaf Harofeh Medical Center.Patient(s): Eighteen with nonobstructive azoospermia in whom testicular sperm was found after testicular sperm extraction.Intervention(s): Testicular sperm retrieval, cryopreservation, and ICSI with fresh or frozenthawed testicular spermatozoa.Main Outcome Measure(s): Two-pronuclear fertilization; embryo cleavage rates, mean number of embryos transferred per cycle, and their relative quality, embryo implantation, clinical pregnancy, and ongoing pregnancy rates (PRs) per ET.Result(s): No statistically significant differences were noted in all parameters examined between ICSI cycles with fresh or cryopreserved testicular spermatozoa from the same nine patients and comparing all ICSI cycles performed; with fresh (25 cycles) and thawed (14 cycles) testicular spermatozoa, respectively: two-pronuclear fertilization, 47% versus 44%; embryo cleavage rates, 94% versus 89%; implantation rates, 9% versus 11%; and clinical PR, 26% versus 27%. The delivery or ongoing PR using fresh sperm was better (21% versus 9%), but the difference did not reach statistical significance. The cumulative clinical PRs and ongoing PRs per testicular sperm extraction procedure were 36% and 24%, respectively.Conclusion(s): Testicular sperm cryopreservation using a simple freezing protocol is promising in patients with nonobstructive azoospermia augmenting the overall success achieved after surgical sperm retrieval. (Fertility Sterility 1997;68:892-7. C 1997 by American Society for Reproductive Medicine.)     

The imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: the role of microvascular growth and abnormalities

In heart failure, a deficient oxygen supply often is a primary cause for myocardial dysfunction. The reverse however, may also be true; the changes that occur in the failing heart may predispose for the existence of tissue hypoxia, which further affects the function of the heart. Specifically, myocardial hypertrophy and accelerated heart rhythm enhance oxygen demand, while supply is hampered short by endothelial dysfunction and diffusion barriers (such as fibrosis, arterial hyperplasia, and myocyte hypertrophy). Another contributory factor may be deficient growth of the microvasculature that does not keep pace with the rate of myocardial hypertrophy. Fewer microvessels have been observed in many forms of cardiomyopathies. On the other hand, some distinct forms of cardiomyopathies are characterized by the compensatory growth of microvessels, or even excess angiogenesis. This review summarizes the knowledge that has been gathered on this topic thus far and discusses factors that mediate myocardial microvessel growth. Furthermore, a paradigm is presented in which the rate of microvessel growth predicts, at least in part, the degree of myocardial dysfunction. Therapies aimed at the restoration of the microcirculation are proposed to preserve and improve myocardial function.     

Matricellular proteins in the heart: possible role during stress and remodeling

Matricellular proteins are extracellular matrix proteins that modulate cell-matrix interactions and cell function, and do not seem to have a direct structural role. The family includes tenascin-C (TN-C), tenascin-X (TN-X), osteonectin, osteopontin, thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2). Expression of matricellular proteins is high during embryogenesis, but almost absent during normal postnatal life. Interestingly, it re-appears in response to injury. Left ventricular remodeling is a complicated process that occurs in the stressed heart, and is still not completely understood. Several members of the matricellular protein family, like tenascin-C, osteopontin, and osteonectin are up-regulated after cardiac injury. Therefore, this group of proteins may have crucial functions in the heart coping with stress. This review will focus on the expression, regulation and function of these matricellular proteins, and will discuss the crucial functions that these proteins might exert during remodeling of the stressed heart.     

Activated leukocytes and endothelial cells enhance retention of ultrasound contrast microspheres containing perfluoropropane in inflamed venules

PURPOSE: To characterize the flow dynamics of albumin ultrasound contrast microspheres containing perfluoropropane (PFP) in normal and inflamed microvasculature. MATERIALS AND METHODS: Mesenteric microvessels of rats were examined after an intravenous injection of fluorocein-labeled erythrocytes or PFP microspheres by fluorescence intravital microscopy with and without local application of 10(-8) M platelet activating factor (PAF) as an experimental form of inflammation. RESULTS: All the microspheres passed freely through arterioles and capillaries. Mean velocities of the microspheres in each vessel were closely correlated with those of erythrocytes. Only a minor fraction of the microspheres was retained in the venules (> or =0.1 s stoppage) by attachment to endothelial cells. The frequency of microsphere retention in venules was significantly enhanced by PAF (2.6+/-2.1%, P<0.01 vs. control), especially in regions with leukocyte adhesion. Treatment with a monoclonal antibody to intercellular adhesion molecule-1, P-selectin or the common leukocyte antigen inhibited PAF-induced microsphere retention in venules (P<0.05). In the inflamed microcirculation, a small subgroup of microspheres becomes attached to venular endothelial cells in regions with leukocyte adhesion via interaction among microspheres, activated leukocytes and endothelial cells via adhesion molecules. CONCLUSION: In inflamed microcirculation, a small subgroup of microspheres becomes attached to venular endothelial cells in regions with leukocyte adhesion via interaction among microspheres, activated leukocytes and endothelial cells via adhesion molecules. These results suggest that ultrasonography with microspheres has the potential to evaluate inflammatory site distribution as well as tissue perfusion.     

IL-1 is required for tumor invasiveness and angiogenesis

Here, we describe that microenvironmental IL-1 beta and, to a lesser extent, IL-1 alpha are required for in vivo angiogenesis and invasiveness of different tumor cells. In IL-1 beta knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared with WT mice. Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1 beta KO mice. The addition of exogenous IL-1 into B16-containing Matrigel plugs in IL-1 beta KO mice partially restored the angiogenic response. Moreover, the incorporation of IL-1 receptor antagonist to B16-containing plugs in WT mice inhibited the ingrowth of blood vessel networks into Matrigel plugs. In IL-1 alpha KO mice, local tumor development and induction of an angiogenic response in Matrigel plugs was less pronounced than in WT mice, but significantly higher than in IL-1 beta KO mice. These effects of host-derived IL-1 alpha and IL-1 beta were not restricted to the melanoma model, but were also observed in DA/3 mammary and prostate cancer cell models. In addition to the in vivo findings, IL-1 contributed to the production of vascular endothelial cell growth factor and tumor necrosis factor in cocultures of peritoneal macrophages and tumor cells. Host-derived IL-1 seems to control tumor angiogenesis and invasiveness. Furthermore, the anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.     

Are triglyceride-rich lipoproteins associated with aortic valve sclerosis? A preliminary report

Background: Evidence linking cardiovascular risk factors to aortic valve sclerosis (AVS) has led to the assumption that the latter is an atherosclerosis-like process. However, triglyceride (TG)-rich lipoproteins, an important risk factor for atherosclerosis, have been rarely investigated in connection with AVS. Methods: A cross-sectional study of 246 healthy individuals (mean age 59±6 years, 77% men) was conducted. Subjects underwent an echocardiographic assessment and extensive blood lipid measurements, including evaluation of TG-related indices, such as serum apolipoprotein (apo) C_II and C_III levels, apo C_III levels in VLDL+LDL particles, and apo C_III ratio (C_III level in HDL/C_III level in VLDL+LDL). Results: Twenty-three patients (9.3%) were diagnosed as having AVS. On average, these patients were 5 years older and had higher levels of serum cholesterol, LDL-C and LP(a), compared with non-AVS subjects. In addition, the AVS patients exhibited higher concentrations of serum apo C_II, serum apo C_III and apo C_III in VLDL+LDL, and a lower apo C_III ratio. Adjusting for age and gender, a 1 S.D. increment in apo C_III in VLDL+LDL was associated with odds ratio (OR) of 1.76 (95% CI: 1.17–2.65) for AVS. Further adjustment for atherosclerotic risk factors did not alter the association appreciably (OR=1.65, 95% CI: 1.06–2.58). Conclusion: TG-rich lipoproteins may be involved in the early development of AVS. Confirmation in prospective studies is required.     

Rapid bedside measurement of brain natriuretic peptide in patients with chronic heart failure

BACKGROUND: Brain natriuretic peptide (BNP) levels have been used to assess clinical status and predict prognosis of patients with chronic heart failure (CHF). However, BNP levels can only be measured in specialized laboratories which has hampered its use in daily clinical practice. We compared a new, rapid, BNP assay with a conventional BNP measurement and evaluated the applicability to current practice by comparing it with standard clinical parameters. METHODS: BNP levels were determined in 78 stable CHF patients and 20 controls. The severity of CHF was assessed by determination of New York Heart Association functional class (NYHA), left ventricular ejection fraction (LVEF) and peak oxygen consumption (peak VO(2)), and these parameters were compared to BNP levels. RESULTS: Overall, rapid BNP assessment was highly correlated with the conventional BNP assay (r=0.95, P<0.0001). In the higher ranges (>200 pmol/l), however, correlation was less accurate, and tended to overestimate. BNP levels also strongly correlated with both NYHA class, LVEF and peak VO(2) (all P<0.001). A cut-off value for BNP of 20 pmol/l yielded a sensitivity of 91% and a specificity of 92% to detect the presence of left ventricular systolic dysfunction. CONCLUSIONS: Rapid measurement of BNP levels is comparable to conventional BNP measurement and strongly correlated to clinical tests that are currently used to stratify CHF patients. Wider use of this method may yield a reduction of costly and time-consuming clinical tests and may reduce the medical burden of CHF.