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Case Reports in Hematology 2023Pyruvate kinase deficiency (PKD) is an autosomal recessive defect of the enzyme pyruvate kinase (PK) which is involved in catalyzing a reaction that produces ATP in the...
Pyruvate kinase deficiency (PKD) is an autosomal recessive defect of the enzyme pyruvate kinase (PK) which is involved in catalyzing a reaction that produces ATP in the glycolytic pathway. It is the most common defect of the glycolytic pathway associated with congenital anemia. Patients usually present with signs of chronic hemolytic anemia such as hyperbilirubinemia, splenomegaly, reticulocytosis, and gallstones; the presentation can vary by age. Diagnosis is usually made by demonstration of decreased PK enzymatic activity in a spectrophotometric assay and on the detection of mutations in the PK-LR gene. Management strategies vary from full splenectomies to hematopoietic stem cell transplants with gene therapies with transfusions and administration of PK-activators coming in between. Thromboembolic complications do occur in patients with splenectomy, but there are not much data regarding this for patients with PKD. We present a case of a patient with PKD who demonstrated priapism to be a thromboembolic complication. This differs greatly as priapism has been frequently reported in patients with other chronic hemoglobinopathies such as sickle cell disease, thalassemia, and G6PD with and without splenectomy. While it is still unclear how splenectomies can result in thrombotic events in PKD, there does appear to be a correlation between splenectomies with resultant thrombocytosis with increased platelet adhesion.
PubMed: 37197195
DOI: 10.1155/2023/6503311 -
Cureus Mar 2023Intracavernosal injection of Trimix (a combination of phentolamine, papaverine, and alprostadil) is used for the treatment of erectile dysfunction. A rare but serious...
Intracavernosal injection of Trimix (a combination of phentolamine, papaverine, and alprostadil) is used for the treatment of erectile dysfunction. A rare but serious side effect of Trimix is priapism, a persistent erection lasting for more than four hours. Penoscrotal decompression is a newer technique being used to treat refractory and persistent ischemic priapism. Here, we report a unique case of priapism treated with penoscrotal decompression in a patient following an unmeasured injection of Trimix. A 36-year-old male presented to the emergency room complaining of a persistent painful erection over the previous five days following a Trimix injection and illicit methamphetamine use. At bedside, aspiration and irrigation were attempted without any improvement. Phenylephrine injection was contraindicated due to sinus tachycardia. The patient then underwent bilateral penoscrotal decompression on day six post-Trimix injection. The procedure was successful with a resolution of the erection, though some moderate corporal fibrosis was noted. At a 10-day follow-up, the patient reported moderate pain in his penis but had regained complete potency. Misuse of Trimix can cause persistent ischemic priapism. Penoscrotal decompression is a novel technique used to treat persistent ischemic priapism and has been shown to have positive efficacy in the resolution of priapism as well as in salvaging erectile function. To our knowledge, treatment of persistent priapism with penoscrotal decompression after using Trimix has not yet been reported in the literature. Given the rarity of this, our report highlights a unique case that has potential benefit for future practitioners who are faced with this clinical scenario.
PubMed: 37123749
DOI: 10.7759/cureus.36757 -
Frontiers in Neurology 2023Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and...
INTRODUCTION
Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI. We tested the hypotheses that (i) elevated CBF, a marker of cerebral hemodynamic compensation in SCD, is associated with global and regional brain atrophy, and (ii) silent cerebral infarct burden is associated with brain atrophy in excess of infarct volume.
METHODS
Healthy controls ( = 49) and SCD participants without overt stroke ( = 88) aged 7-32 years completed 3 T brain MRI; pseudocontinuous arterial spin labeling measured CBF. Multivariable linear regressions assessed associations of independent variables with GMV, WMV, and volumes of cortical/subcortical regions.
RESULTS
Reduced hemoglobin was associated with reductions in both GMV ( = 0.032) and WMV ( = 0.005); reduced arterial oxygen content (CaO) was also associated with reductions in GMV ( = 0.035) and WMV ( = 0.006). Elevated gray matter CBF was associated with reduced WMV ( = 0.018). Infarct burden was associated with reductions in WMV 30-fold greater than the infarct volume itself ( = 0.005). Increased GM CBF correlated with volumetric reductions of the insula and left and right caudate nuclei ( = 0.017, 0.017, 0.036, respectively). Infarct burden was associated with reduced left and right nucleus accumbens, right thalamus, and anterior corpus callosum volumes ( = 0.002, 0.002, 0.009, 0.002, respectively).
DISCUSSION
We demonstrate that anemia and decreased CaO2 are associated with reductions in GMV and WMV in SCD. Increased CBF and infarct burden were also associated with reduced volume in subcortical structures. Global WMV deficits associated with infarct burden far exceed infarct volume itself. Hemodynamic compensation via increased cerebral blood flow in SCD seems inadequate to prevent brain volume loss. Our work highlights that silent cerebral infarcts are just a portion of the brain injury that occurs in SCD; brain volume is another potential biomarker of brain injury in SCD.
PubMed: 37064181
DOI: 10.3389/fneur.2023.1112865 -
Asian Journal of Urology Apr 2023
PubMed: 36942118
DOI: 10.1016/j.ajur.2021.12.009 -
Blood Advances Jul 2023
Topics: Humans; Anemia, Sickle Cell; Pain
PubMed: 36883847
DOI: 10.1182/bloodadvances.2022008965 -
Frontiers in Molecular Biosciences 2023Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. , often referred to as the Brazilian...
Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. , often referred to as the Brazilian wandering spider, banana spider or "armed" spider, is endemic to South America and amongst the most dangerous venomous spiders in the world. There are 4,000 envenomation accidents with each year in Brazil, which can lead to symptoms including priapism, hypertension, blurred vision, sweating, and vomiting. In addition to its clinical relevance, venom contains peptides that provide therapeutic effects in a range of disease models. In this study, we explored the neuroactivity and molecular diversity of venom using fractionation-guided high-throughput cellular assays coupled to proteomics and multi-pharmacology activity to broaden the knowledge about this venom and its therapeutic potential and provide a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We coupled proteomics with ion channel assays using a neuroblastoma cell line to identify venom compounds that modulate the activity of voltage-gated sodium and calcium channels, as well as the nicotinic acetylcholine receptor. Our data revealed that venom is highly complex compared to other neurotoxin-rich venoms and contains potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the reported neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides for which their activity and molecular target remains to be determined. Our findings provide a platform for studying the bioactivity of known and novel neuroactive components in the venom of and other spiders and suggest that our discovery pipeline can be used to identify ion channel-targeting venom peptides with potential as pharmacological tools and to drug leads.
PubMed: 36865382
DOI: 10.3389/fmolb.2023.1069764 -
Urology Case Reports Mar 2023Ischemic priapism is a urologic emergency requiring urgent intervention to prevent tissue necrosis and preserve erectile function. Cases refractory to aspiration and...
Ischemic priapism is a urologic emergency requiring urgent intervention to prevent tissue necrosis and preserve erectile function. Cases refractory to aspiration and intra-cavernosal sympathomimetic therapy requires timely surgical shunting. Corpus cavernosum abscess following penile shunts is an exceedingly rare complication, with as few as 2 previous reported cases. We report our experience and outcome in the case of a 50-year-old patient who developed a corpora cavernosum abscess and concurrent corporoglanular fistula, following penile shunt procedures for ischemic priapism.
PubMed: 36860418
DOI: 10.1016/j.eucr.2023.102341 -
Diseases (Basel, Switzerland) Feb 2023Priapism is a very rare complication of malignancy and is usually accompanied by locally advanced or widely metastatic disease. We describe a case of priapism arising in...
BACKGROUND
Priapism is a very rare complication of malignancy and is usually accompanied by locally advanced or widely metastatic disease. We describe a case of priapism arising in a 46-year-old male with localised rectal cancer that was responding to therapy.
CASE PRESENTATION
This patient had just completed two weeks of neoadjuvant, long-course chemoradiation when he presented with persistent painful penile erection. Assessment and diagnosis were delayed for more than 60 h, and although a cause could not be determined from imaging, a near complete radiological response of the primary rectal cancer was seen. His symptoms were refractory to urologic intervention and were associated with extreme psychological distress. He re-presented shortly thereafter with extensively metastatic disease in the lungs, liver, pelvis, scrotum, and penis; additionally, multiple venous thromboses were identified, including in the dorsal penile veins. His priapism was not reversible and was associated with a considerable symptom burden for the remainder of his life. His malignancy did not respond to first-line palliative chemotherapy or radiation, and his clinical course was further complicated by obstructive nephropathy, ileus, and genital skin breakdown with a suspected infection. We initiated comfort measures, and he ultimately died in hospital less than five months after his initial presentation.
CONCLUSION
Priapism in cancer is usually related to tumour infiltration of the penis and corporal bodies resulting in poor venous and lymphatic drainage. The management is palliative and can include chemotherapy, radiation, surgical shunting, and potentially penectomy; however, conservative penis-sparing therapy may be reasonable in patients with limited life expectancy.
PubMed: 36810548
DOI: 10.3390/diseases11010034 -
Blood Advances Jul 2023Sickle cell hemoglobin SC (HbSC) disease is the second most frequent sickle cell disease (SCD) genotype after sickle cell anemia (HbSS). Globally, ∼55 000 newborns...
Sickle cell hemoglobin SC (HbSC) disease is the second most frequent sickle cell disease (SCD) genotype after sickle cell anemia (HbSS). Globally, ∼55 000 newborns with HbSC are delivered annually, with the highest HbC gene frequency in West Africa. In Ghana, 40% of adults visiting the Ghana Institute of Clinical Genetics SCD clinic have HbSC. Unlike HbSS, hydroxyurea use is not routinely recommended for individuals with HbSC because of the perceived high-risk to benefit ratio. To test the hypothesis that at least 5% of adults with HbSC will meet the American Society of Hematology criteria for severe disease, we conducted a retrospective descriptive cohort study of all individuals with HbSC (≥18 years) who visited the clinic in 2019. Adults with HbSC aged from 18 to 45 years were selected. We identified a comparison group of 639 individuals with HbSS and matched the frequency based on the age and sex of individuals with HbSC. Severe disease was defined as a history of ≥3 SCD-associated moderate or severe pain episodes per year, history of acute chest syndrome, and severe symptomatic chronic anemia that interferes with daily activities or quality of life. The study end points were the proportion of individuals with SCD who met the definition of severe disease and were eligible for hydroxyurea. In total, 64 of 639 (10.0%) individuals with HbSC met the eligibility criteria for hydroxyurea therapy compared with 154 of 639 (24.1%) individuals with HbSS. Less than 1% and 3% of individuals with severe HbSC and HbSS, respectively, were routinely prescribed with hydroxyurea in this tertiary care medical center.
Topics: Infant, Newborn; Adult; Humans; Hydroxyurea; Retrospective Studies; Cohort Studies; Quality of Life; Hemoglobin SC Disease; Anemia, Sickle Cell; Hemoglobin, Sickle
PubMed: 36799926
DOI: 10.1182/bloodadvances.2022009049