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JAMA Cardiology May 2023Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency...
IMPORTANCE
Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important.
OBJECTIVE
To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy.
DATA SOURCES
A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials.
STUDY SELECTION
Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up.
DATA EXTRACTION AND SYNTHESIS
Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials.
MAIN OUTCOMES AND MEASURES
The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups.
RESULTS
A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups.
CONCLUSIONS AND RELEVANCE
Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.
Topics: Humans; Male; Middle Aged; Antihypertensive Agents; Sympathectomy; Treatment Outcome; Hypertension; Kidney; Hypotension
PubMed: 36853627
DOI: 10.1001/jamacardio.2023.0338 -
Journal of Ayurveda and Integrative... 2022The superficial infection that involves the hair follicle with bogginess or induration of involved parts of the scalp along with pustules, erosions, crusts, ulcers, and...
INTRODUCTION
The superficial infection that involves the hair follicle with bogginess or induration of involved parts of the scalp along with pustules, erosions, crusts, ulcers, and scales resulting in hair fall is known as folliculitis decalvans (FD). This condition accounts for approximately 11% of all cases with primary cicatricial alopecia. Based on clinical features like Keshadhwansha (hair fall) with Harsha (hypersensitivity), Kandu (itching), Toda (pain), FD can be correlated with Raktaja Krimi Vikara (RKV).
OBSERVATION AND RESULTS
A 24 years' male patient with the chief complaint of patchy hair loss in the scalp region associated with scale formation, itching, and pain for 2 months. He had a history of pustules-like eruption over the frontal and parietal regions. He tried various topical and oral medications for 8 days but didn't get any sign of improvement and came to NIA hospital for Ayurveda treatment. Due to the signs like pustules over the scalp, hair loss with honey-colored crusting, scarring, mild itching, and pain; he was diagnosed with RKV ∼ FD. After treatment with Ayurveda medicine and leech therapy, complete remission of the scar, lesions, itching, pain, and hair loss was obtained, and there was new hair growth over the scalp with normal distribution. The patient was on follow-up for 33 months with no signs of itching, pain, and hair fall.
CONCLUSION
Complete remission of FD was achieved by Ayurveda medicine along with Jalaukavacharana and it seems highly effective on the basis of remission period compared to contemporary treatment modalities. It is suggested to have further clinical studies with large samples to analyze its effectiveness.
PubMed: 36436296
DOI: 10.1016/j.jaim.2022.100673 -
Heart Failure Reviews May 2022Despite advances in the overall management of acute myocardial infarction (AMI), cardiogenic shock in the setting of AMI (CS-AMI) continues to be associated with poor... (Review)
Review
Despite advances in the overall management of acute myocardial infarction (AMI), cardiogenic shock in the setting of AMI (CS-AMI) continues to be associated with poor patient outcomes. There are multiple devices that can be used in CS-AMI to support the failing circulation, although their utility in improving outcomes as compared with conventional pharmacotherapy of vasopressors and inotropes remains to be established. This contemporary review provides an update on the evidence base for each of these techniques. In CS-AMI, acute thrombotic occlusion of a major epicardial artery leads to hypoxia and myocardial ischaemia in the territory subtended by that vessel. The resultant regional dysfunction in myocardial contractility can severely compromise stroke volume and result in acute circulatory failure, systemic hypoperfusion, lactic acidosis, multi-organ failure and ultimately death.
Topics: Heart-Assist Devices; Humans; Intra-Aortic Balloon Pumping; Myocardial Infarction; Shock, Cardiogenic; Stroke Volume; Treatment Outcome
PubMed: 33655387
DOI: 10.1007/s10741-021-10088-8 -
Protein Science : a Publication of the... Dec 2023Hirudin from Hirudo medicinalis is a bivalent α-Thrombin (αT) inhibitor, targeting the enzyme active site and exosite-I, and is currently used in anticoagulant therapy...
From haemadin to haemanorm: Synthesis and characterization of full-length haemadin from the leech Haemadipsa sylvestris and of a novel bivalent, highly potent thrombin inhibitor (haemanorm).
Hirudin from Hirudo medicinalis is a bivalent α-Thrombin (αT) inhibitor, targeting the enzyme active site and exosite-I, and is currently used in anticoagulant therapy along with its simplified analogue hirulog. Haemadin, a small protein (57 amino acids) isolated from the land-living leech Haemadipsa sylvestris, selectively inhibits αT with a potency identical to that of recombinant hirudin (K = 0.2 pM), with which it shares a common disulfide topology and overall fold. At variance with hirudin, haemadin targets exosite-II and therefore (besides the free protease) it also blocks thrombomodulin-bound αT without inhibiting the active intermediate meizothrombin, thus offering potential advantages over hirudin. Here, we produced in reasonably high yields and pharmaceutical purity (>98%) wild-type haemadin and the oxidation resistant Met5 → nor-Leucine analogue, both inhibiting αT with a K of 0.2 pM. Thereafter, we used site-directed mutagenesis, spectroscopic, ligand-displacement, and Hydrogen/Deuterium Exchange-Mass Spectrometry techniques to map the αT regions relevant for the interaction with full-length haemadin and with the synthetic N- and C-terminal peptides Haem(1-10) and Haem(45-57). Haem(1-10) competitively binds to/inhibits αT active site (K = 1.9 μM) and its potency was enhanced by 10-fold after Phe3 → β-Naphthylalanine exchange. Conversely to full-length haemadin, haem(45-57) displays intrinsic affinity for exosite-I (K = 1.6 μM). Hence, we synthesized a peptide in which the sequences 1-9 and 45-57 were joined together through a 3-Glycine spacer to yield haemanorm, a highly potent (K = 0.8 nM) inhibitor targeting αT active site and exosite-I. Haemanorm can be regarded as a novel class of hirulog-like αT inhibitors with potential pharmacological applications.
Topics: Hirudins; Thrombin; Amino Acid Sequence; Peptides; Heme
PubMed: 37924304
DOI: 10.1002/pro.4825 -
Emergency Medicine Journal : EMJ Jul 2021
Topics: Adolescent; Adolescent Behavior; Emergency Medicine; Humans; Professional-Patient Relations; Trauma Centers; Wounds and Injuries
PubMed: 33785486
DOI: 10.1136/emermed-2020-211105 -
Cureus Feb 2020A 58-year-old male presented to the emergency department with a chief complaint of knee pain and swelling after performing hirudotherapy (leech therapy) approximately...
A 58-year-old male presented to the emergency department with a chief complaint of knee pain and swelling after performing hirudotherapy (leech therapy) approximately one week prior. Knee arthrocentesis demonstrated significant hemarthrosis. Hirudotherapy is being used for a broad array of reasons including treatment of osteoarthritis, to plastic and reconstructive surgery. Case reports and journal articles often discuss cutaneous reactions, bleeding, and infection as common adverse events. Intra-articular bleeding is not commonly mentioned. With hirudotherapy being utilized more as alternative therapy for osteoarthritis and joint pain, physicians should be aware of hemarthrosis as a possible adverse reaction.
PubMed: 32190470
DOI: 10.7759/cureus.6915 -
Frontiers in Endocrinology 2024Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective... (Review)
Review
Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective treatments for DN, and the prognosis for patients remains poor. Hirudin, one of the primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, and anti-inflammatory properties, exhibiting significant protective effects on the kidneys. In recent years, there has been a surge of interest in studying the potential benefits of hirudin, especially in its role in the management of DN. This article delves into the mechanisms by which hirudin contributes to the treatment of DN and its clinical efficacy.
Topics: Animals; Humans; Diabetic Nephropathies; Hirudins; Kidney; Medicine, Chinese Traditional; Leeches; Diabetes Mellitus
PubMed: 38344666
DOI: 10.3389/fendo.2024.1296843 -
Surgical Infections Mar 2020Infections with spp. are a recognized complication of leech therapy for circulatory complications in replanted digits. Ciprofloxacin is commonly used empirically for...
Infections with spp. are a recognized complication of leech therapy for circulatory complications in replanted digits. Ciprofloxacin is commonly used empirically for coverage in such cases. Evolving resistance patterns of should be considered in designing an antibiotic strategy. Three consecutive patients with complicated replantations had site cultures yielding isolates resistant to ciprofloxacin. These cultures were analyzed to identify effective antibiotic agents. Each isolate, and each additional site organism, was sensitive to cefepime. Our routine antibiotic coverage for leech application has been changed to cefepime. sensitivities and resistances should be monitored to adapt to future changes in appropriate antibiotics.
Topics: Aeromonas; Anti-Bacterial Agents; Cefepime; Ciprofloxacin; Drug Resistance, Microbial; Humans; Leeching; Microbial Sensitivity Tests; Replantation
PubMed: 31556841
DOI: 10.1089/sur.2019.067 -
Journal of Molecular Biology Mar 2020Harnessing the translational potential of the GLP-1/GLP-1R system in pancreatic beta cells has led to the development of established GLP-1R-based therapies for the... (Review)
Review
Harnessing the translational potential of the GLP-1/GLP-1R system in pancreatic beta cells has led to the development of established GLP-1R-based therapies for the long-term preservation of beta cell function. In this review, we discuss recent advances in the current research on the GLP-1/GLP-1R system in beta cells, including the regulation of signaling by endocytic trafficking as well as the application of concepts such as signal bias, allosteric modulation, dual agonism, polymorphic receptor variants, spatial compartmentalization of cAMP signaling and new downstream signaling targets involved in the control of beta cell function.
Topics: Animals; Cyclic AMP; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Insulin; Insulin Secretion; Insulin-Secreting Cells; Polymorphism, Single Nucleotide; Signal Transduction
PubMed: 31446075
DOI: 10.1016/j.jmb.2019.08.009 -
Journal of Global Antimicrobial... Dec 2020Aeromonas sp. infections are a recognized complication of medical leech therapy (MLT). In patients requiring MLT, ciprofloxacin or trimethoprim-sulphamethoxazole are...
Multidrug resistant Aeromonas infection following medical leech therapy: A case report and development of a joint antimicrobial stewardship and infection prevention protocol.
OBJECTIVE
Aeromonas sp. infections are a recognized complication of medical leech therapy (MLT). In patients requiring MLT, ciprofloxacin or trimethoprim-sulphamethoxazole are commonly used to prevent such nosocomial infections. After a patient at our institution developed a MLT-associated multi-drug resistant (MDR) Aeromonas infection, we developed and evaluated a joint antimicrobial stewardship and infection prevention protocol for MLT at our institution.
METHODS
We describe a case of a surgical site infection with MDR Aeromonas following MLT that was resistant to typically prescribed prophylactic antimicrobials, and development of a new leech culture protocol to proactively monitor for antimicrobial resistance among our institution's leech supply. We also report the rates of MLT-associated infections prior to and following implementation of this protocol and the antimicrobial susceptibility profiles detected in leech culture at our institution.
RESULTS
Between October 2014 and February 2018, 46 patients received MLT at our institution. Other than the case described in this report, no other instances of MLT-related infections were noted during this time period. Culture results from 22 leeches in six batches since February 2018 showed that all were susceptible to ciprofloxacin, TMP-SMX, and ceftriaxone. Since initiation of a leech culture protocol, no further cases of MLT-associated infections have been reported at our institution.
CONCLUSIONS
In light of increasing antimicrobial resistance and the potentially devastating consequences of MLT-associated infections, institutions offering MLT should be aware of these risks and ensure that protocols are in place to minimize infection risks for patients.
Topics: Aeromonas; Animals; Anti-Bacterial Agents; Antimicrobial Stewardship; Gram-Negative Bacterial Infections; Humans; Leeches; Leeching
PubMed: 33137533
DOI: 10.1016/j.jgar.2020.10.010