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Journal of Medical Case Reports Aug 2022Low blood pressure and associated postural symptoms are well-recognized manifestations of anaphylaxis. Nonetheless, anaphylaxis can present with high blood pressure and...
BACKGROUND
Low blood pressure and associated postural symptoms are well-recognized manifestations of anaphylaxis. Nonetheless, anaphylaxis can present with high blood pressure and is rarely reported in the literature. We report an unusual presentation of anaphylaxis with severe supine hypertension and orthostatic intolerance.
CASE PRESENTATION
A 43-year-old Asian female presented to the emergency department with generalized itching, hives, and postural dizziness after taking a slow-release diclofenac sodium 100 mg tablet. On admission, the patient was tachycardic with a supine blood pressure of 200/100 mmHg. She had urticaria and bilateral rhonchi. A clinical diagnosis of anaphylaxis was made. She was treated with intravenous hydrocortisone and chlorpheniramine, but intramuscular adrenaline was withheld owing to her high blood pressure. She was kept in the supine position, and her vital parameters were closely monitored. Although the respiratory and cutaneous symptoms improved with treatment, her blood pressure remained elevated. Forty minutes later, the postural dizziness recurred as she sat up on the bed and her blood pressure plummeted from 198/100 mmHg to 80/60 mmHg. She was put back in the supine position immediately, and the blood pressure was restored with three doses of intramuscular adrenaline and a fluid bolus. Her postural symptoms completely resolved after adrenaline, but her blood pressure remained elevated. Two weeks after the initial presentation, a diagnosis of essential hypertension was made, which probably had been undetected. In anaphylaxis, where the cardiovascular system is involved, a blood pressure reduction from baseline is expected in patients with preexisting hypertension. Despite cardiovascular involvement, our patients' blood pressure on presentation to the emergency department was much higher than her pretreatment ambulatory blood pressure, thus making this presentation unusual.
CONCLUSIONS
Diagnosis and treatment of anaphylaxis can be delayed in patients presenting with high blood pressure. Postural symptoms should alert the clinician to cardiovascular involvement despite elevated supine blood pressure. Early treatment with adrenaline should be considered in these patients with extreme caution.
Topics: Adult; Anaphylaxis; Blood Pressure Monitoring, Ambulatory; Dizziness; Epinephrine; Female; Humans; Hypertension; Hypotension
PubMed: 36008817
DOI: 10.1186/s13256-022-03528-y -
Arthritis Research & Therapy Aug 2022Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR...
A multicentre, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase (MIRROR): 12-month efficacy, safety, immunogenicity, and pharmacokinetic findings during long-term extension of an open-label study.
BACKGROUND
Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month pegloticase + methotrexate co-therapy responder rate of 79%, compared to an established 42% pegloticase monotherapy responder rate. Longer-term efficacy/safety data are presented here.
METHODS
Uncontrolled gout patients (serum urate [SU] ≥ 6 mg/dL and SU ≥ 6 mg/dL despite urate-lowering therapy [ULT], ULT intolerance, or functionally-limiting tophi) were included. Patients with immunocompromised status, G6PD deficiency, severe kidney disease, or methotrexate contraindication were excluded. Oral methotrexate (15 mg/week) and folic acid (1 mg/day) were administered 4 weeks before and during pegloticase therapy. Twelve-month responder rate (SU < 6 mg/dL for ≥ 80% during month 12), 52-week change from baseline in SU, and extended safety were examined. Efficacy analyses were performed for patients receiving ≥ 1 pegloticase infusion. Pharmacokinetics (PK)/anti-drug antibodies (ADAs) were examined and related to efficacy/safety findings.
RESULTS
Fourteen patients were included (all male, 49.3 ± 8.7 years, 13.8 ± 7.4-year gout history, pre-therapy SU 9.2 ± 2.5 mg/dL). Three patients were non-responders and discontinued study treatment before 24 weeks, one patient exited the study per protocol at 24 weeks (enrolled prior to treatment extension amendment), and 10 remained in the study through week 52. Of the 10, 8 completed 52 weeks of pegloticase + methotrexate and were 12-month responders. The remaining two discontinued pegloticase + methotrexate at week 24 (met treatment goals) and stayed in the study under observation (allopurinol prescribed at physicians' discretion); one remained a responder at 12 months. At 52 weeks, change from baseline in SU was - 8.2 ± 4.1 mg/dL (SU 1.1 ± 2.4 mg/dL, n = 10). Gout flares were common early in treatment but progressively decreased while on therapy (weeks 1-12, 13/14 [92.9%]; weeks 36-52, 2/8 [25.0%]). One patient recovered from sepsis (serious AE). Two non-responders developed high ADA titers; fewer patients had trough concentrations (C) below the quantitation limit (BQL), and the median C was higher (1.03 µg/mL vs. BQL) than pegloticase monotherapy trials.
CONCLUSIONS
Pegloticase + methotrexate co-therapy was well-tolerated over 12 months, with sustained SU lowering, progressive gout flare reduction, and no new safety concerns. Antibody/PK findings suggest methotrexate attenuates ADA formation, coincident with higher treatment response rates.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03635957 . Registered on 17 August 2018.
Topics: Gout; Gout Suppressants; Humans; Male; Methotrexate; Polyethylene Glycols; Symptom Flare Up; Treatment Outcome; Urate Oxidase; Uric Acid
PubMed: 36008814
DOI: 10.1186/s13075-022-02865-z -
PloS One 2022Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood.
METHODS
In this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice.
RESULTS
Obese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice.
CONCLUSIONS
Unhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis.
Topics: Animals; Carcinoma, Hepatocellular; Cholesterol; Choline; Diet, High-Fat; Disease Models, Animal; Disease Progression; Female; Fructose; Liver; Liver Neoplasms; Male; Mice; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity
PubMed: 35994501
DOI: 10.1371/journal.pone.0272623 -
The International Journal on Drug Policy Oct 2022Significant declines in drinking among young people have been recorded in many high-income countries over the past 20 years. This analysis explored the role of gender -...
INTRODUCTION
Significant declines in drinking among young people have been recorded in many high-income countries over the past 20 years. This analysis explored the role of gender - which we interpret as socially constructed and relational - to provide insight into whether and how gender might be implicated in declining youth drinking.
METHODS
Interview data from four independent qualitative studies from Australia, Denmark, Sweden and the UK (n=194; participants aged 15-19 years) were analysed by researchers in each country following agreement about analytical focus. Findings were collated by the lead author in a process of 'qualitative synthesis' which involved successive rounds of data synthesis and feedback from the broader research team.
FINDINGS
Our analysis raised two notable points in relation to the role of gender in declining youth drinking. The first concerned the consistency and vehemence across three of the countries at which drinkers and states of intoxication were pejoratively described in gendered terms (e.g., bitchy, sleazy). The second related to the opportunities non- and light-drinking offered for expressing alternate and desirable configurations of femininities and masculinities.
CONCLUSIONS
We identified an intolerance towards regressive constructions of gender that emphasise weakness for women and strength for men and a valorisation of gendered expressions of maturity through controlled drinking. Though subtle differences in gendered drinking practices between and within countries were observed, our findings offer insight into how young people's enactions of gender are embedded in, and evolve alongside, these large declines in youth drinking.
Topics: Adolescent; Alcohol Drinking; Female; Humans; Income; Male; Masculinity; Qualitative Research; Underage Drinking
PubMed: 35985206
DOI: 10.1016/j.drugpo.2022.103827 -
Molecular Metabolism Oct 2022The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (MNADK) mediates de novo mitochondrial NADP biosynthesis by catalyzing the phosphorylation of NAD to...
OBJECTIVE
The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (MNADK) mediates de novo mitochondrial NADP biosynthesis by catalyzing the phosphorylation of NAD to yield NADP. In this study, we investigated the function and mechanistic basis by which MNADK regulates metabolic homeostasis.
METHODS
Generalized gene set analysis by aggregating human patient genomic databases, metabolic studies with genetically engineered animal models, mitochondrial bioenergetic analysis, as well as gain- and loss- of-function studies were performed to address the functions and mechanistic basis by which MNADK regulates energy metabolism and redox state associated with metabolic disease.
RESULTS
Human MNADK common gene variants or decreased expression of the gene are significantly associated with the occurrence of type-2 diabetes, non-alcoholic fatty liver disease (NAFLD), or hepatocellular carcinoma (HCC). Ablation of the MNADK gene in mice led to decreased fat oxidation, coincident with increased respiratory exchange ratio (RER) and decreased energy expenditure upon energy demand triggered by endurance exercise or fasting. On an atherogenic high-fat diet (HFD), MNADK-null mice exhibited hepatic insulin resistance and glucose intolerance, indicating a type-2 diabetes-like phenotype in the absence of MNADK. MNADK deficiency led to a decrease in mitochondrial NADP(H) but an increase in cellular reactive oxygen species (ROS) in mouse livers. Consistently, protein levels of the major metabolic regulators or enzymes were decreased, while their acetylation modifications were increased in the livers of MNADK-null mice. Feeding mice with a HFD caused S-nitrosylation (SNO) modification, a posttranslational modification that represses protein activities, on MNADK protein in the liver. Reconstitution of an SNO-resistant MNADK variant, MNADK-S193, into MNADK-null mice mitigated hepatic steatosis induced by HFD.
CONCLUSION
MNADK, the only known mammalian mitochondrial NAD kinase, plays important roles in preserving energy homeostasis to mitigate the risk of metabolic disorders.
Topics: Animals; Carcinoma, Hepatocellular; Diabetes Mellitus, Type 2; Humans; Liver Neoplasms; Mice; Mice, Knockout; Mitochondria; Mitochondrial Proteins; NAD; NADP; Non-alcoholic Fatty Liver Disease; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 35944895
DOI: 10.1016/j.molmet.2022.101562 -
Cancer Medicine Jan 2023Allergic reactions to pegaspargase during ALL therapy are typically due to antibodies against polyethylene glycol (PEG), which is also used as a stabilizing agent in...
OBJECTIVE
Allergic reactions to pegaspargase during ALL therapy are typically due to antibodies against polyethylene glycol (PEG), which is also used as a stabilizing agent in mRNA-based SARS-CoV-2 vaccines. To evaluate the safety of these vaccines in patients with anti-pegaspargase antibodies.
METHODS
We retrospectively reviewed the records of patients treated for ALL who had received SARS-CoV-2 vaccinations. All patients had antibodies against pegaspargase assayed during ALL therapy prospectively and in response to clinical allergies. Symptoms of intolerance to vaccination were gathered retrospectively from chart abstraction.
RESULTS
SARS-CoV-2 vaccination was well tolerated in all 78 patients with prior exposure to pegaspargase as part of their leukemia therapy. No reactions were observed in the 54 patients without a history of anti-pegaspargase antibodies or in 19 patients with antibodies who received mRNA vaccination. 1 patient who received the polysorbate containing Janssen vaccine experienced mild symptoms after vaccination not meeting the criteria of clinical allergy which spontaneously resolved within 25 minutes.
CONCLUSION
SARS-CoV-2 vaccination is safe in this population.
Topics: Humans; Antibodies; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Polyethylene Glycols; Retrospective Studies; RNA, Messenger; SARS-CoV-2; Vaccines
PubMed: 35837830
DOI: 10.1002/cam4.5011 -
BMC Pregnancy and Childbirth Jun 2022Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy. It is characterized by high risk of adverse outcomes for the mother...
BACKGROUND
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy. It is characterized by high risk of adverse outcomes for the mother and the foetus, if not adequately controlled. The aim of the study was to evaluate the effects of 4000 mg of myoinositol supplementation in women with GDM on maternal-foetal outcomes, compared to controls.
METHODS
A cohort of 330 women with GDM, 150 supplemented with myoinositol and 180 controls were enrolled. Clinical and metabolic parameters and the prevalence of maternal and foetal complications were assessed.
RESULTS
The same number of women in the two groups started insulin as additional therapy. Women treated with myoinositol more frequently had a long-acting insulin scheme of treatment than those untreated (p<0.001), while women untreated with myoinositol more frequently had a basal-bolus insulin regimen (p<0.001) compared to women on myoinositol. Patients treated with myoinositol had significantly lower fasting plasma glucose (p=0.032), post-prandial dinner glucose (p=0.014), insulin requirement both in the 2nd and in the 3rd trimesters (p=0.001 and p<0.001, respectively), than those not treated with myoinositol. With regard to maternal/foetal outcomes, lower birth weight (p=0.043) and frequency of hypoglycaemic events (p=0.001) were observed in women treated with myoinositol compared to controls.
CONCLUSIONS
Women with GDM treated with myoinositol showed an improved glycaemic control in the 3 trimester of pregnancy and a lower insulin requirement, when insulin was added to the treatment, compared to controls. In addition, they showed lower preterm birth weight and neonatal hypoglycaemia, compared to women not supplemented with myoinositol.
Topics: Blood Glucose; Diabetes, Gestational; Dietary Supplements; Female; Glycemic Control; Humans; Infant, Newborn; Inositol; Insulin; Pregnancy; Premature Birth
PubMed: 35754028
DOI: 10.1186/s12884-022-04852-3 -
Neuropsychopharmacology Reports Sep 2022Although resistance to thyroid hormone beta (RTHβ) is associated with attention-deficit/hyperactivity disorder, there are few reports of other concomitant mood...
BACKGROUND
Although resistance to thyroid hormone beta (RTHβ) is associated with attention-deficit/hyperactivity disorder, there are few reports of other concomitant mood disorders in individuals with RTHβ.
CASE PRESENTATION
A 67-year-old woman who had been previously diagnosed with RTHβ (Refetoff syndrome) came to our department as a depressed patient. She was hospitalized twice for depression and treated with antidepressants both times. Paroxetine (37.5 mg/day) treatment during the first hospitalization did not cause any side effects, but treatment with mirtazapine (15 mg/day) and venlafaxine (150 mg/day) during the second hospitalization caused clonus and disturbance of consciousness, and these adverse effects resulted in a prolonged period of hospitalization. Finally, the patient's symptoms were controlled with quetiapine (75 mg/day).
CONCLUSION
Poor tolerability to antidepressants was observed, which may be related to thyroid hormone intolerance. Low doses of quetiapine may contribute to improvements in depression.
Topics: Aged; Antidepressive Agents; Female; Humans; Mirtazapine; Mood Disorders; Mutation; Paroxetine; Quetiapine Fumarate; Thyroid Hormone Receptors beta; Thyroid Hormone Resistance Syndrome; Thyroid Hormones; Venlafaxine Hydrochloride
PubMed: 35748411
DOI: 10.1002/npr2.12280 -
Diabetes Care Aug 2022To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.
OBJECTIVE
To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.
RESEARCH DESIGN AND METHODS
We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality.
RESULTS
In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82-1.30), 1.23 (1.07-1.42), and 1.61 (1.30-2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92-1.18), 1.12 (1.06-1.18), and 1.15 (1.09-1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2-34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15-17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44-77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters.
CONCLUSIONS
Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity.
Topics: Adult; Blood Glucose; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus; Female; Humans; Insulin Resistance; Male; Obesity; Prediabetic State; Prospective Studies; Risk Factors
PubMed: 35700159
DOI: 10.2337/dc22-0202 -
Cureus May 2022Lactose intolerance (LI) appears usually in later ages when the lactase enzyme becomes deficient or absent in the small intestine. Conflicting results have been reported...
BACKGROUND
Lactose intolerance (LI) appears usually in later ages when the lactase enzyme becomes deficient or absent in the small intestine. Conflicting results have been reported in the literature about the association of lactose intolerance with various gastrointestinal malignancies. Hence, our aim was to study the association between LI, colon cancer (CCa), and gastric cancer (GC) using a large database.
METHODS
A cross-sectional study was performed using the National Inpatient Sample (NIS) database between 2004 and 2014. We identified adult patients (18-90 years) who were diagnosed with LI (study group) using appropriate International Classification of Diseases, Ninth Revision (ICD-9) codes. The control group comprised patients who did not have a diagnosis of LI. We identified the diagnosis of CCa and GC in both study and control groups using the ICD-9 codes. Univariable and multivariable logistic regression analyses were performed to assess the association between LI, CCa, and GC.
RESULTS
The total population comprised 71,360,501 patients, of which 57,909 (0.08%) were diagnosed with LI. LI patients were older (62 vs 51 years) with more females (61.5% vs 60.1%) and less African American patients (11.8% vs 14.3%) (p <0.0001 for all). In addition, LI patients had more smoking (12.4% vs 12%) and obesity (15% vs 8.9%). On the other hand, patients in the LI group had less alcohol use (3.8% vs 4.2%) (p <0.0001). After adjusting for the age, gender, race, smoking, alcohol, obesity, and inflammatory bowel disease, the LI group had a slightly lower rate of CCa (OR 0 .974, 95%CI 0.906-1.048, p = 0.486) and a lower rate of GC (OR: 0.993, 95%CI 0.924-1.068, p =0.853); however, the results were not statistically significant.
CONCLUSION
Patients with lactose intolerance may have a lower risk of colon and gastric cancer. However, these findings were not statistically significant. Further studies are needed to understand this association.
PubMed: 35676992
DOI: 10.7759/cureus.24713