-
Frontiers in Oncology 2024Essential Thrombocythemia is a chronic myeloproliferative neoplasm characterized by an isolated excessive production of platelets. Extreme thrombocytosis is defined by...
BACKGROUND
Essential Thrombocythemia is a chronic myeloproliferative neoplasm characterized by an isolated excessive production of platelets. Extreme thrombocytosis is defined by having a platelet count greater than or equal to 1,000 x 10/L, which may lead to the development of acquired von Willebrand syndrome and complications of excessive hemorrhage.
CASE DESCRIPTION
A 74-year-old female patient was brought in for a bone marrow examination regarding elevated platelet count. She had no history of excessive bleeding. The physical exam was unremarkable with no petechiae or hematomas. Complete blood count showed platelet count 1,491x10/L. Bone marrow aspiration and biopsy were unremarkable, however, the patient developed bleeding from the biopsy site. Local pressure and an ice pack were ineffective, so she received 20 mcg of desmopressin subcutaneously, 1 unit of fresh frozen plasma and was started on tranexamic acid 1,000 mg orally every 8 hours. She was admitted for bleeding control and had another dose of desmopressin. Blood work showed elevated partial thromboplastin time and normal international normalized ratio. Acquired von Willebrand syndrome was suspected and a sample for von Willebrand disease was sent out. The next day her bleeding continued, and her Hb decreased from 145 to 89 g/L, she became symptomatic (tachycardic) and fatigued. The coagulation profile was consistent with acquired von Willebrand syndrome. Since she continued bleeding, she received 1 unit of packed red blood cells. A high dose of hydroxyurea (3g/day) was started urgently; within 24 hours platelet count was halved, and the bleeding resolved. Blood work was repeated 24 hours later and showed normalization of partial thromboplastin time and a normal Von Willebrand profile.
CONCLUSION
Patients with extreme thrombocytosis are at high risk of bleeding due to acquired Von Willebrand Syndrome. Initiation of hydroxyurea at the time of bone marrow exam helps to control platelet count and minimizes the risk of peri-procedural hemorrhage in high-risk Essential Thrombocythemia patients with suspected acquired Von Willebrand Syndrome.
PubMed: 38361779
DOI: 10.3389/fonc.2024.1326209 -
Frontiers in Endocrinology 2024We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome... (Meta-Analysis)
Meta-Analysis
UNLABELLED
We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome (EAS). A systematic review of studies on diagnostic test accuracy in patients with CD, NNH, or EAS subjected to the desmopressin test obtained from LILACS, PubMed, EMBASE, and CENTRAL databases was performed. Two reviewers independently selected the studies, assessed the risk of bias, and extracted the data. Hierarchical and bivariate models on Stata software were used for meta-analytical summaries. The certainty of evidence was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation Working Group) approach. In total, 14 studies were included: 3 studies on differentiated CD versus NNH and 11 studies on differentiated CD versus EAS. Considering ΔACTH in 8 studies involving 429 patients, the pooled sensitivity for distinguishing CD from EAS was 0.85 (95% confidence interval [CI]: 0.80-0.89, I2 = 17.6%) and specificity was 0.64 (95% CI: 0.49-0.76, I2 = 9.46%). Regarding Δcortisol in 6 studies involving 233 participants, the sensitivity for distinguishing CD from EAS was 0.81 (95% CI: 0.74-0.87, I2 = 7.98%) and specificity was 0.80 (95% CI: 0.61-0.91, I2 = 12.89%). The sensitivity and specificity of the combination of ΔACTH > 35% and Δcortisol > 20% in 5 studies involving 511 participants were 0.88 (95% CI: 0.79-0.93, I2 = 35%) and 0.74 (95% CI: 0.55-0.87, I2 = 27%), respectively. The pooled sensitivity for distinguishing CD from NNH in 3 studies involving 170 participants was 0.88 (95% CI: 0.79-0.93) and the specificity was 0.94 (95% CI: 0.86-0.97). Based on the desmopressin test for differentiating CD from EAS, considering ΔACTH, Δcortisol, or both percent increments, 15%, 19%, or 20% of patients with CD, respectively, would be incorrectly classified as having EAS. For CD versus NNH, 11% of patients with CD would be falsely diagnosed as having NNH, whereas 7% of patients with NNH would be falsely diagnosed as having CD. However, in all hierarchical plots, the prediction intervals were considerably wider than the confidence intervals. This indicates low confidence in the estimated accuracy, and the true accuracy is likely to be different.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85634, identifier CRD42018085634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68317, identifier CRD42017068317.
Topics: Humans; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; ACTH Syndrome, Ectopic; Pituitary ACTH Hypersecretion
PubMed: 38352712
DOI: 10.3389/fendo.2024.1332120 -
Problemy Endokrinologii Jan 2024To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to...
[Diagnostic value of bilateral inferior petrosal sinus sampling in various modifications and methods of radiation and radionuclide imaging in the diagnosis and differential diagnosis of ACTH-dependent endogenous hypercortisolism].
AIM
To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to control catheter position with or without the ACTH/prolactin normalized ratio calculation in the differential diagnosis of ACTH-dependent endogenous hypercortisolism, and the diagnostics performance of ectopic ACTH-syndrome (EAS) visualization.
MATERIALS AND METHODS
A single-center diagnostic study with a retrospective analysis of the data was carried out. The study included patients with ACTH-dependent endogenous hypercorticism with no visualization of pituitary adenoma on MRI or adenoma sizes less than 6 mm. All patients underwent BIPSS with and without calculation of the ACTH/prolactin normalized ratio. Visualization of an EAS included pituitary MRI (to exclude EAS), whole-body CT scan with contrast, and somatostatin receptor scintigraphy with 99mTc-Tectrotide and CT (99mTc-Tectrotide SPECT). The final verification was based on immunohistochemical confirmation of the tumor or stable remission of Cushing's disease (CD) after surgical treatment. Statistical data processing was carried out by using IBM SPSS Statistics 23. Confidence intervals were calculated using the JavaStat online calculator.
RESULTS
230 BIPSS were performed in 228 patients (166 women, 62 men), of which 178 patients were verified as CD and 50 cases were EAS of various localization. The effectiveness of catheterization of petrosal sinuses was 96.9%. The sensitivity of BIPSS without ACTH/prolactin ratio calculation (n=70) was 95.9% (95% CI 86.3-98.9), specificity was 92% (95% CI 75.0-97.8), for the BIPSS with additional determination of ACTH/prolactin-normalized ratio (n=51) - 97.3% (95% CI 86.2-99.5) and 93.8% (95% CI 71.7-98.9), respectively. The use of the MRI method for this sample of patients had a sensitivity of 60.2% (95% CI 52.6-67.5), specificity of 59.2% (95% CI 44.2-73.0), the total body CT with contrast has a sensitivity of 74% (95% CI 59.7-85.4), specificity of 100% (95% CI 97.95-100). The diagnostic accuracy for 99mTc-Tectrotide SPECT in NET visualization has a sensitivity of 73.3% (95% CI 44.9-92.2), specificity of 100% (95% CI 95.3-100).
CONCLUSION
BIPSS with desmopressin stimulation and prolactin measurements to control catheter position, as well as the additional calculation of the ACTH/prolactin-normalized ratio, is an optimal method for the differential diagnosis of EAS. Patients who are identified an EAS on BIPSS may be further referred for 99mTc-Tectrotide SPECT and CT for tumor visualization.
Topics: Male; Humans; Female; Cushing Syndrome; Petrosal Sinus Sampling; Deamino Arginine Vasopressin; Retrospective Studies; Diagnosis, Differential; Prolactin; Pituitary ACTH Hypersecretion; ACTH Syndrome, Ectopic; Radionuclide Imaging; Adenoma; Adrenocorticotropic Hormone
PubMed: 38311990
DOI: 10.14341/probl13299 -
Endocrine Journal Apr 2024Hyponatremia leads to severe central nervous system disorders and requires immediate treatment in some cases. However, a rapid increase in serum sodium (s-Na)...
Hyponatremia leads to severe central nervous system disorders and requires immediate treatment in some cases. However, a rapid increase in serum sodium (s-Na) concentration could cause osmotic demyelination syndrome. To achieve a safety hyponatremia treatment, we develop a prediction model of s-Na concentration using a machine learning. Among the 341 and 47 patients admitted to two tertiary hospitals for hyponatremia treatment (s-Na <130 mEq/L), those who were admitted to the general unit with urine sodium <20 mEq/L or treated with desmopressin were excluded. Ultimately, 74 and 15 patients (342 and 146 6-hourly datasets) were included in the learning and validation data, respectively. We trained the prediction model using three regression algorithms for shallow machine learning to predict s-Na every 6 h during treatment with the data of patients with hyponatremia (median s-Na: 112.5 mEq/L; range: 110.0-116.8 mEq/L) from one hospital. The model was validated externally using the data of patients with hyponatremia (median s-Na: 117.0 mEq/L; range: 112.9-120.0 mEq/L) from another hospital. Using 5-7 predictors (water intake, sodium intake, potassium intake, urine volume, s-Na concentration, serum potassium concentration, serum chloride concentration), the support vector regression model showed the best performance overall (root mean square error = 0.05396; R = 0.92), followed by the linear regression and regression tree models. The predicted s-Na levels, using explainable machine learning algorithms and clinically accessible parameters, correlated well with the actual levels. Thus, our model could be applied to the treatment of hyponatremia in clinical practice.
Topics: Hyponatremia; Humans; Male; Female; Machine Learning; Aged; Sodium; Middle Aged; Adult; Aged, 80 and over; Treatment Outcome; Algorithms
PubMed: 38311418
DOI: 10.1507/endocrj.EJ23-0561 -
Journal of Medical Case Reports Feb 2024The kidney biopsy is a routine procedure. Once an indication has been established, the benefit-risk balance may be considered. Sometimes, even with effective treatment,...
BACKGROUND
The kidney biopsy is a routine procedure. Once an indication has been established, the benefit-risk balance may be considered. Sometimes, even with effective treatment, a severe complication may develop.
CASE PRESENTATION
We present the case of a Caucasian 20-year-old young woman admitted to investigating and treating acute kidney injury. Renal involvement was characterized by kidney damage requiring hemodialysis treatment, positive immunologic testing, 0.5 g/day proteinuria, and microscopic hematuria. Contraindications were excluded, so an ultrasound-guided kidney biopsy was performed. To reduce the bleeding complication, Octostim (desmopressin) was administered. There were no direct complications following the kidney biopsy, so we continued the immunosuppressive treatment. Histologically founded thrombotic microangiopathy. However, 1 week later, severe bleeding developed with the need for urgent surgical left kidney removal.
CONCLUSION
Kidney biopsy can be considered a routine procedure, and various bleeding episodes are most common in terms of complications, the detection of which is essential. Delayed bleeding complications are rare and can be caused by minor injuries. Our young patient had no injury during the hospitalization. We hypothesized that the developed serious and delayed bleeding complication resulted from effective immunosuppressive treatment. To the best of our knowledge, this is the first such case to date. However, renal biopsy in the case of thrombotic microangiopathy requires caution.
Topics: Female; Humans; Young Adult; Adult; Kidney; Nephrectomy; Thrombotic Microangiopathies; Acute Kidney Injury; Image-Guided Biopsy; Immunosuppressive Agents; Biopsy
PubMed: 38308348
DOI: 10.1186/s13256-023-04338-6 -
Cureus Jan 2024Hypernatremia has been significantly associated with in-hospital mortality and discharge to long-term care facilities. The appropriate correction of electrolyte...
Hypernatremia has been significantly associated with in-hospital mortality and discharge to long-term care facilities. The appropriate correction of electrolyte disturbances, especially sodium, is important to consider to prevent the addition of central nervous system disturbances, such as cerebral edema and eventual brain injury. The importance of maintaining a proper correction of hypernatremia has been well studied and used in clinical practice. Choosing to use a hypotonic solution is a key principle. It is of utmost importance to adjust the rate of correction based on the patient's symptoms, underlying etiology, and associated comorbidities. This case demonstrates how a correction formula was used and adjusted accordingly in an 81-year-old female with severe hypernatremia and metabolic encephalopathy with multiple comorbidities, including hypopituitarism. It is noteworthy to examine the correction rate, how it was calculated and delivered, and how the main cause of the hypernatremia was determined. Considering all these factors can help to properly administer any additional corrective medications, such as desmopressin (DDAVP) in a patient with diabetes insipidus (DI) secondary to hypopituitarism, or adjust the correcting rate based on signs, symptoms, and laboratory findings.
PubMed: 38298322
DOI: 10.7759/cureus.51474 -
Perioperative Medicine (London, England) Jan 2024We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing... (Review)
Review
We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.
PubMed: 38263259
DOI: 10.1186/s13741-023-00358-4 -
International Journal of Molecular... Jan 2024Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago.... (Review)
Review
Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.
Topics: Humans; Gastrointestinal Agents; Insulin; Cell-Penetrating Peptides; Biological Availability; Hydrogels
PubMed: 38255888
DOI: 10.3390/ijms25020815 -
The Cochrane Database of Systematic... Jan 2024Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care.
OBJECTIVES
To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology.
SEARCH METHODS
We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP).
SELECTION CRITERIA
We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.
DATA COLLECTION AND ANALYSIS
We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received.
MAIN RESULTS
We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials).
AUTHORS' CONCLUSIONS
We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.
Topics: Male; Female; Adult; Humans; Tranexamic Acid; Aprotinin; Deamino Arginine Vasopressin; Network Meta-Analysis; Hemorrhage; Aminocaproic Acid; Stroke; Orthopedic Procedures; Fibrin
PubMed: 38226724
DOI: 10.1002/14651858.CD013295.pub2