Abstract Background Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic ...features of 108 subjects. Methods Between September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US. Results Most subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks. Conclusions Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.
The acute hepatic porphyrias are a group of four inherited disorders, each resulting from a deficiency in the activity of a specific enzyme in the heme biosynthetic pathway. These disorders present ...clinically with acute neurovisceral symptoms which may be sporadic or recurrent and, when severe, can be life‐threatening. The diagnosis is often missed or delayed as the clinical features resemble other more common medical conditions. There are four major subgroups: symptomatic patients with sporadic attacks (<4 attacks/year) or recurrent acute attacks (≥4 attacks/year), asymptomatic high porphyrin precursor excretors, and asymptomatic latent patients without symptoms or porphyrin precursor elevations. Given their clinical heterogeneity and potential for significant morbidity with suboptimal management, comprehensive clinical guidelines for initial evaluation, follow‐up, and long‐term management are needed, particularly because no guidelines exist for monitoring disease progression or response to treatment. The Porphyrias Consortium of the National Institutes of Health's Rare Diseases Clinical Research Network, which consists of expert centers in the clinical management of these disorders, has formulated these recommendations. These recommendations are based on the literature, ongoing natural history studies, and extensive clinical experience. Initial assessments should include diagnostic confirmation by biochemical testing, subsequent genetic testing to determine the specific acute hepatic porphyria, and a complete medical history and physical examination. Newly diagnosed patients should be counseled about avoiding known precipitating factors. The frequency of follow‐up depends on the clinical subgroup, with close monitoring of patients with recurrent attacks who may require treatment modifications as well as those with clinical complications. Comprehensive care should include subspecialist referrals when needed. Annual assessments include biochemical testing and monitoring for long‐term complications. These guidelines provide a framework for monitoring patients with acute hepatic porphyrias to ensure optimal outcomes. (Hepatology 2017;66:1314‐1322)
The acute porphyrias, 4 inherited disorders of heme biosynthesis, cause life-threatening attacks of neurovisceral symptoms that mimic many other acute medical and psychiatric conditions. Lack of ...clinical recognition often delays effective treatment, and inappropriate diagnostic tests may lead to misdiagnosis and inappropriate treatment. We review the clinical manifestations, pathophysiology, and genetics of the acute porphyrias and provide recommendations for diagnosis and treatment on the basis of reviews of the literature and clinical experience. An acute porphyria should be considered in many patients with unexplained abdominal pain or other characteristic symptoms. The diagnosis can be rapidly confirmed by demonstration of a markedly increased urinary porphobilinogen level by using a single-void urine specimen. This specimen should also be saved for quantitative measurement of porphobilinogen, 5-aminolevulinic acid, and total porphyrin levels. Intravenous hemin therapy, started as soon as possible, is the most effective treatment. Intravenous glucose alone is appropriate only for mild attacks (mild pain, no paresis or hyponatremia) or until hemin is available. Precipitating factors should be eliminated, and appropriate supportive and symptomatic therapy should be initiated. Prompt diagnosis and treatment greatly improve prognosis and may prevent development of severe or chronic neuropathic symptoms. We recommend identification of at-risk relatives through enzymatic or gene studies.
The Current Evidence for Marijuana as Medical Treatment Buck, J Stewart; Bloomer, Ainsley K; Wally, Meghan K ...
Journal of bone and joint surgery. American volume,
2020-December-2, 2020-Dec-02, 2020-12-2, Letnik:
102, Številka:
23
Journal Article
Recenzirano
➤ At present, the growth of public and political support for the use of marijuana as a medical treatment is outpacing the growth of scientific evidence.
➤ Despite limited evidence, marijuana-based ...compounds (including cannabidiol) are promoted as alternatives to opioid pain medication in the treatment of ongoing bodily pain for which people seek care.
➤ Clinical research on the medical applications of marijuana-based compounds is limited by federal regulations, and most commercially available products are not available to researchers for study.
Background:
The management of displaced intraarticular calcaneus fractures (DIACFs) is a difficult problem with disappointing results from open reduction internal fixation (ORIF). Alternatively, ORIF ...with primary subtalar arthrodesis (PSTA) has gained increasing popularity. The purpose of this study is to review patient-centered and radiographic outcomes of ORIF plus PSTA using only screws through a sinus tarsi approach.
Methods:
A retrospective study of patients who underwent ORIF+PSTA for DIACFs was conducted. The same surgical technique was used in all cases consisting of only screws; no plates were used. Delayed surgeries past 8 weeks were excluded. Demographic and radiographic data were collected including worker’s compensation claims. Plain radiographs were used to characterize injuries and review outcomes.
Results:
Seventy-nine DIACFs underwent PSTA with a median follow-up of 200 days (n = 69 patients). Median time to weightbearing was 57.5 days postoperatively. Ten fractures were documented as Sanders II, 36 as Sanders III, and 32 as Sanders IV. Sixty-eight fractures (86.1%) achieved fusion on radiographs at a median of 126.5 (range, 54-518) days. Thirty-nine fractures (57.3%) demonstrated radiographic fusion in all 3 predefined locations. Nine of the 14 worker’s compensation patients returned to work within the period of observation. There were 8 complications: 3 requiring a secondary operation. Eleven of 79 fractures treated did not go on to achieve radiographic union.
Conclusion:
In this retrospective case series, we found that screws-only primary subtalar arthrodesis for the treatment of DIACFs through a sinus tarsi approach was associated with relatively high rates of return to work and radiographic fusion.
Level of Evidence:
Level IV, retrospective case series.
In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients ...will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post‐transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13‐56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15‐29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5‐year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival. (Liver Transpl 2005;11:1590–1596.)
Laboratory diagnosis of erythropoietic protoporphyria (EPP) requires a marked increase in total erythrocyte protoporphyrin (300-5000 μg/dL erythrocytes, reference interval <80 μg/dL) and a ...predominance (85%-100%) of metal-free protoporphyrin normal, mostly zinc protoporphyrin (reference intervals for the zinc protoporphyrin proportion have not been established); plasma porphyrins are not always increased. X-linked protoporphyria (XLP) causes a similar increase in total erythrocyte protoporphyrin with a lower fraction of metal-free protoporphyrin (50%-85% of the total).
In studying more than 180 patients with EPP and XLP, the Porphyrias Consortium found that erythrocyte protoporphyrin concentrations for some patients were much higher (4.3- to 46.7-fold) than indicated by previous reports provided by these patients. The discrepant earlier reports, which sometimes caused the diagnosis to be missed initially, were from laboratories that measure protoporphyrin only by hematofluorometry, which is intended primarily to screen for lead poisoning. However, the instrument can calculate results on the basis of assumed hematocrits and reports results as "free" and "zinc" protoporphyrin (with different reference intervals), implying separate measurements of metal-free and zinc protoporphyrin. Such misleading reports impair diagnosis and monitoring of patients with protoporphyria.
We suggest that laboratories should prioritize testing for EPP and XLP, because accurate measurement of erythrocyte total and metal-free protoporphyrin is essential for diagnosis and monitoring of these conditions, but less important for other disorders. Terms and abbreviations used in reporting erythrocyte protoporphyrin results should be accurately defined.
Erythropoietic protoporphyria (EPP), the most common porphyria of childhood and the third most common porphyria of adulthood, is characterized clinically by painful, non-blistering cutaneous ...photosensitivity. Two distinct inheritance patterns involving mutations affecting genes that encode enzymes of the heme biosynthetic pathway underlie the clinical phenotype. Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms. Isoniazid (INH) is widely used for treatment of latent and active M. tuberculosis (TB). Sideroblastic anemia is observed in some patients taking INH, and studies have shown that this process is a consequence of inhibition of ALAS2 by INH. Based on these observations, we postulated that INH might have therapeutic activity in patients with EPP. We challenged this hypothesis in a murine model of EPP and showed that, after 4 weeks of treatment with INH, both plasma PPIX and hepatic PPIX were significantly reduced. Next, we tested the effect of INH on patients with EPP. After eight weeks, no significant difference in plasma or red cell PPIX was observed among the 15 patients enrolled in the study. These results demonstrate that while INH can lower PPIX in an animal model of EPP, the standard dose used to treat TB is insufficient to affect levels in humans.
Erythropoietic protoporphyria is a disorder of heme synthesis in which deficient ferrochelatase activity leads to excess production and biliary excretion of protoporphyrin. The main clinical ...features, photosensitivity and hepatobiliary disease that may progress to liver failure, are caused by the toxicity of protoporphyrin. Liver transplantation has been used to treat liver failure in erythropoietic protoporphyria, but excess production of protoporphyrin by the bone marrow continues causing recurrence of liver disease in the majority of patients. This is the first report of successful sequential liver and bone marrow transplantation in a patient with liver failure as a result of erythropoietic protoporphyria. This combination corrected the severe phenotype, resolving the severe photosensitivity and halting erythropoietic protoporphyria associated liver graft injury. Splenectomy seemed to facilitate the successful bone marrow transplant.
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