1,721,337 research outputs found
Thiazide diuretics are back in CKD: the case of chlorthalidone
No full textSodium and volume excess is the fundamental risk factor underlying hypertension in chronic kidney disease (CKD) patients, who represent the prototypical population characterized by salt-sensitive hypertension. Low salt diets and diuretics constitute the centrepiece for blood pressure control in CKD. In patients with CKD stage 4, loop diuretics are generally preferred to thiazides. Furthermore, thiazide diuretics have long been held as being of limited efficacy in this population. In this review, by systematically appraising published randomized trials of thiazides in CKD, we show that this class of drugs may be useful even among people with advanced CKD. Thiazides cause a negative sodium balance and reduce body fluids by 1–2 l within the first 2–4 weeks and these effects go along with improvement in hypertension control. The recent CLICK trial has documented the antihypertensive efficacy of chlorthalidone, a long-acting thiazide-like diuretic, in stage 4 CKD patients with poorly controlled hypertension. Overall, chlorthalidone use could be considered in patients with treatment-resistant hypertension when spironolactone cannot be administered or must be withdrawn due to side effects. Hyponatremia, hypokalaemia, volume depletion and acute kidney injury are side effects that demand a vigilant attitude by physicians prescribing these drugs. Well-powered randomized trials assessing hard outcomes are still necessary to more confidently recommend the use of these drugs in advanced CKD
Safety of non-vitamin K antagonist oral anticoagulants: concerns in patients with atrial fibrillation and glomerular hyperfiltration?
No full textPharmacokinetic relevance of glomerular hyperfiltration for drug dosing
No full textIn chronic kidney disease (CKD) patients, hypofiltration may lead to the accumulation of drugs that are cleared mainly by the kidney and, vice versa, hyperfiltration may cause augmented renal excretion of the same drugs. In this review we mainly focus on the issue of whether hyperfiltration significantly impacts the renal clearance of drugs and whether the same alteration may demand an up-titration of the doses applied in clinical practice. About half of severely ill, septic patients and patients with burns show glomerular hyperfiltration and this may lead to enhanced removal of drugs such as hydrophilic antibiotics and a higher risk of antibiotic treatment failure. In general, hyperfiltering obese individuals show higher absolute drug clearances than non-obese control subjects, but this depends on the body size descriptor adopted to adjust for fat excess. Several mechanisms influence pharmacokinetics in type 2 diabetes, including renal hyperfiltration, reduced tubular reabsorption and augmented tubular excretion. However, no consistent pharmacokinetic alteration has been identified in hyperfiltering obese subjects and type 2 diabetics. Non-vitamin K antagonist oral anticoagulants (NOACs) have exhibited lower plasma concentrations in hyperfiltering patients in some studies in patients with atrial fibrillation, but a recent systematic review failed to document any excess risk for stroke and systemic embolism in these patients. Hyperfiltration is common among severely ill patients in intensive care units and drug levels should be measured whenever possible in these high-risk patients to prevent underdosing and treatment failure. Hyperfiltration is also common in patients with obesity or type 2 diabetes, but no consistent pharmacokinetic alteration has been described in these patients. No NOAC dose adjustment is indicated in patients with atrial fibrillation being treated with these drugs
New trials in resistant hypertension: mixed blessing stories
No full textResistant hypertension (RH) is linked to an increased risk of cardiovascular and renal complications. Treatment options include non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive drug combinations, including diuretics. Renal denervation is another option for treatment-resistant hypertension. New compounds targeting different pathways involved in RH-including inhibitors of aminopeptidase A, endothelin antagonists and selective aldosterone synthase inhibitors-have been tested in clinical trials in this condition. The centrally acting drug firibastat, targeting the brain renin-angiotensin system, failed to demonstrate significant effectiveness in reducing blood pressure (BP) in patients with difficult-to-treat and RH in the Firibistat in Resistant Hypertension (FRESH) trial. Aprocitentan, a dual endothelin A and B receptor antagonist, showed a moderate but statistically significant decrease in BP in patients with RH in the Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension (PRECISION) trial. However, concerns remain about potential adverse events, such as fluid retention. The use of baxdrostat, a selective aldosterone synthase inhibitor, showed promising results in reducing BP in patients with treatment-resistant hypertension in the Baxdrostat in Resistant Hypertension (BrigHTN) trial. However, a subsequent trial, HALO, failed to meet its primary endpoint. The unexpected results may be influenced by factors such as patient adherence and white-coat hypertension. Despite the disappointing results from HALO, the potential benefits of inhibiting aldosterone synthesis remain to be fully understood. In conclusion, managing RH remains challenging, and new compounds like firibastat, aprocitentan and baxdrostat have shown varied effectiveness. Further research is needed to improve our understanding and treatment of this condition
Stress shielding around press-fit radial head arthroplasty: proposal for a new classification system based on the analysis of 97 patients with a mid-term follow-up and a review of the literature
Full text linkStress shielding (SS) around press-fit radial head arthroplasty (RHA) was recently reported as a cause of a new type of proximal radial neck resorption (PRNR). Very few studies have analyzed this phenomenon. No comprehensive classification is currently available. We thus decided to clinically and radiographically analyze 97 patients who underwent a press-fit RHA and who were followed up for a mean period of 72 months (range: 2-14 years). PRNR in the four quadrants of the radial neck was assessed. We designed a novel SS classification based on (1) the degree of resorption of the length of the radial neck and (2) the number of neck quadrants involved on the axial plane. The mean PRNR (mPRNR) was calculated as the mean resorption in the four quadrants. mPRNR was classified as mild (<3 mm), moderate (3 to 6 mm), and severe (>6 mm). Eighty-four percent of the patients presented PRNR. mPRNR was mild in 33% of the patients, moderate in 54%, and severe in 13%. In total, 6% of the patients with mild mPRNR displayed resorption in one quadrant, 18% displayed resorption in two quadrants, 4% displayed resorption in three quadrants, and 72% displayed resorption in four quadrants. All four quadrants were always involved in moderate or severe mPRNR, with no significant differences being detected between quadrants (p = 0.568). mPRNR has no apparent effect on the clinical results, complications, or RHA survival in the medium term. However, longer-term studies are needed to determine the effects of varying degrees of PRNR on implant failure
Pelvic ring reconstruction with tibial allograft, screws and rods following enneking type I and IV resection of primary bone tumors
No full textIntroduction: Surgery of primary malignant tumors involving the sacroiliac joint requires wide resection, which often interrupts the pelvic ring. Nowadays, restoration of the pelvic ring to provide stability and which technique is most fitting remain subject to debate. The aim of this study is to evaluate the results of pelvic reconstruction with pedicle screw instrumentation and tibial allograft following Enneking Type I-IV resections. Patients and methods: All patients who underwent reconstruction with tibial allograft, screws and rods after resection of areas I and IV for primary bone tumors between 2017 and 2022 were reviewed. Clinical and radiological characteristics, fusion rate and functional results were analyzed. The MSTS score and the TESS were used to evaluate functional results. Results: Seven patients were included in the study. Chondrosarcoma was the most common histology. Only four patients reported pain. No fractures were observed at tumor diagnosis. Computer-assisted navigation was used in six cases. Reconstruction was performed in four cases with a screw inserted in the homolateral L5 pedicle and in the ischium, in two cases with a screw in the homolateral L4 pedicle and another in the homolateral L5 pedicle, in the last case with two screws inserted in L4 and L5, one screw in the ischium and another one in the residual iliac wing. In this case a contralateral stabilization was also carried out. The spine screws and the iliac screws were connected with a rod. The mean follow-up for all 7 patients was 37 months. One patient (16.6%) died due to general complications not directly related to the surgery; while the others are alive and apparently free of disease. Complete fusion was obtained in four out of seven patients and the average time for fusion was 9 months. The average MSTS score and TESS were 58.7% and 57.8%, respectively. Discussion: The need for reconstruction is thoroughly debated in literature. The advantages of restoring posterior pelvis stability are the prevention of long-term pain associated with limb shortening and secondary scoliosis. Reestablishment of the pelvic ring can be achieved through synthetic, biologic or hybrid reconstructions. Conclusions: More studies that assess the surgical consequences at long-term follow-up and help clarify the indications for reconstruction and the specific technique are necessary to confirm our preliminary results
The giant cell tumor during pregnancy: a review of literature
No full textBackground: Giant cell tumors (GTC) of bone are benign, locally aggressive tumors generally occurring in young people with a female predominance during reproductive age. Considering their worsening during pregnancy it has been suggested that pregnancy can accelerate GCT progression or favor recurrence but correlation between tumor growth and pregnancy has not yet been clarified. Aim of this study was to clarify clinical characteristics, timing and type of treatment through a literature review on GTCs occurring during pregnancy.Patients and methods: An electronic search was performed in December 2020 in PubMed, Scopus, Embase, Medline, Cochrane Register using the keywords "giant cell tumor" AND "pregnancy" looking for papers reporting cases of giant cell tumors of the bone onset or recurred during pregnancy. The electronic search identified 212 papers; sixteen studies were selected, for a total of 32 cases.Results: The diagnosis was made during pregnancy in 24 cases and after the partum in 8 cases. 27 cases were new diagnoses while 5 cases were recurrences. Pulmonary metastases were reported in 3 patients. The treatment was performed during the pregnancy in 7 out of 32 cases; in the remaining 27 cases treatment was performed after delivery. The hormone receptor status was reported in 14 patients. Data regarding follow-up was reported for 26 out of 32 patients; three patients had local recurrences that were treated with wide resection and amputation in 2 and 1 case, respectively; at the last follow-up all patients were apparently without any evidence of disease except for three patients who had stable lung metastases.Discussion: In case of GCT during pregnancy, a multidisciplinary approach is necessary to offer the patients the best treatment in terms of mother and child's health. A correct diagnosis is necessary and not confusing tumor symptoms with ones of pregnancy is mandatory in order not to delay the diagnosis and let the tumor progress. Actually, even though pregnancy would seem to promote GCT growth and aggressiveness, the relationship is not clear. More studies are necessary to clarify this interesting aspect. Level of Evidence: IV, systematic review. & COPY; 2022 Published by Elsevier Masson SAS
Decongestion in patients with advanced chronic kidney disease coexisting with heart failure
No full textHeart failure (HF) and chronic kidney disease (CKD) are closely interconnected conditions. Congestion, a central element in HF and CKD pathophysiology, progresses from haemodynamic changes to pulmonary oedema, with asymptomatic pulmonary congestion and an isolated increase in brain natriuretic peptide (BNP) as an intermediate step. Management strategies include sodium restriction, diuretics and emerging technologies for fluid monitoring. Diuretics, while essential, present challenges such as resistance and side effects, necessitating combination therapies and alternatives, like SGLT-2 inhibitors and, in special cases, ultrafiltration. Personalized approaches are critical to improving clinical outcomes in HF and CKD
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