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Frontiers in Neurology 2021Ketogenic diet therapies (KDT) are high-fat, low carbohydrate diets used as an effective treatment option for drug-resistant epilepsy. There is limited research on the...
Ketogenic diet therapies (KDT) are high-fat, low carbohydrate diets used as an effective treatment option for drug-resistant epilepsy. There is limited research on the efficacy of KDT for super-refractory status epilepticus (SRSE). We systematically review evidence for use of KDT in children with SRSE and present a single UK tertiary centre's experience. Thirty one articles were included, of which 24 were "medium" or "low" quality. One hundred and forty seven children with SRSE started KDT, of which 141 (96%) achieved ketosis. KDT was started mean 5.3 days (range 1-420) after status epilepticus (SE) started. SRSE resolved in 85/141 (60%) children after mean 6.3 days (range 0-19) post SE onset, but it is unclear whether further treatments were initiated post-KDT. 13/141 (9%) children died. Response to KDT was more likely when initiated earlier ( = 0.03) and in females ( = 0.01). Adverse side effects were reported in 48/141 (34%), mostly gastrointestinal; potentially serious adverse effects occurred in ≤4%. Eight children with SRSE, all diagnosed with febrile infection-related epilepsy syndrome, were treated with KDT at Great Ormond Street Hospital for Children. KDT was initiated enterally at mean day 13.6+/- 5.1 of admission. Seven of 8 (88%) children reported adverse side effects, which were potentially serious in 4/8 (50%), including metabolic acidosis, hypoglycaemia and raised amylase. SE ceased in 6/8 (75%) children after mean 25+/- 9.4 days post onset, but other treatments were often started concomitantly and all children started other treatments post-KDT. Two of 8 (25%) children died during admission and another died post-admission. Four of the remaining 5 children continue to have drug-resistant seizures, one of whom remains on KDT; seizure burden was unknown for one child. Our findings indicate that KDT is possible and safe in children with SRSE. Cessation of SRSE may occur in almost two-thirds of children initiated with KDT, but a causal effect is difficult to determine due to concomitant treatments, treatments started post-KDT and the variable length of time post-KDT onset when SRSE cessation occurs. Given that serious adverse side effects seem rare and response rates are (cautiously) favorable, KDT should be considered as an early treatment option in this group.
PubMed: 33776895
DOI: 10.3389/fneur.2021.643105 -
Scandinavian Journal of Gastroenterology Jul 2021To review clinical and laboratory findings in patients with SARS-Cov-2 (COVID-19) related acute pancreatitis.
OBJECTIVES
To review clinical and laboratory findings in patients with SARS-Cov-2 (COVID-19) related acute pancreatitis.
METHODS
This systematic review was based on a database search for articles of COVID-19 related acute pancreatitis in adult patients with confirmed COVID-19 infection that included age, gender, presenting symptoms, the onset of symptoms, laboratory values, imaging findings and exclusion of common causes of pancreatitis.
RESULTS
Altogether 35 articles comprising 37 patients were included. Acute pancreatitis was the first presentation of COVID-19 in 43% of patients, concurrent with general or respiratory symptoms in 14% of patients or delayed after general or pulmonary symptoms by an average of 10 ± 5 d (range, 1 - 19 d) in 43% of patients. Serum amylase and lipase levels were elevated in 87% and 100% of patients. In 50% and 84%, amylase and lipase levels exceeded three-fold the upper normal limit. Pancreatic necrosis was reported in 6% of patients and in 12% of patients, the pancreas appeared normal. Three patients died.
CONCLUSIONS
We conclude that the bi-modal pattern of the onset of symptoms supports both the cytotoxic and the immune-related pathogenesis of the pancreatic injury. Acute pancreatitis may be the first symptom of COVID-19 infection. Necrosis of the pancreas is rare.
Topics: Acute Disease; Adult; Amylases; COVID-19; Humans; Lipase; Pancreas; Pancreatitis; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 33989101
DOI: 10.1080/00365521.2021.1922751 -
The Cochrane Database of Systematic... Dec 2016The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines... (Meta-Analysis)
Meta-Analysis Review
Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.
BACKGROUND
The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010.
OBJECTIVES
To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children.
SEARCH METHODS
We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV.
DATA COLLECTION AND ANALYSIS
Two review authors assessed each reference for inclusion using exclusion criteria that we had established a priori. Two review authors independently extracted data from each included trial using a standardized data extraction form. We analysed data on an intention-to-treat basis. We performed subgroup analyses for concurrent treatment for tuberculosis and dosage of NVP. We followed standard Cochrane methodological procedures.
MAIN RESULTS
Twelve RCTs, which included 3278 participants, met our inclusion criteria. None of these trials included children. The length of follow-up time, study settings, and NRTI combination drugs varied greatly. In five included trials, participants were receiving concurrent treatment for tuberculosis.There was little or no difference between EFV and NVP in virological success (RR 1.04, 95% CI 0.99 to 1.09; 10 trials, 2438 participants; high quality evidence), probably little or no difference in mortality (RR 0.84, 95% CI 0.59 to 1.19; 8 trials, 2317 participants; moderate quality evidence) and progression to AIDS (RR 1.23, 95% CI 0.72 to 2.11; 5 trials, 2005 participants; moderate quality evidence). We are uncertain whether there is a difference in all severe adverse events (RR 0.91, 95% CI 0.71 to 1.18; 8 trials, 2329 participants; very low quality evidence). There is probably little or no difference in discontinuation rate (RR 0.93, 95% CI 0.69 to 1.25; 9 trials, 2384 participants; moderate quality evidence) and change in CD4 count (MD -3.03; 95% CI -17.41 to 11.35; 9 trials, 1829 participants; moderate quality evidence). There may be little or no difference in treatment failure (RR 0.97, 95% CI 0.76 to 1.24; 5 trials, 737 participants; low quality evidence). Development of drug resistance is probably slightly less in the EFV arms (RR 0.76, 95% CI 0.60 to 0.95; 4 trials, 988 participants; moderate quality evidence). No studies were found that looked at sexual transmission of HIV.When we examined the adverse events individually, EFV probably is associated with more people with impaired mental function (7 per 1000) compared to NVP (2 per 1000; RR 4.46, 95% CI 1.65 to 12.03; 6 trials, 2049 participants; moderate quality evidence) but fewer people with elevated transaminases (RR 0.52, 95% CI 0.35 to 0.78; 3 trials, 1299 participants; high quality evidence), fewer people with neutropenia (RR 0.48, 95% CI 0.28 to 0.82; 3 trials, 1799 participants; high quality evidence), and probably fewer people withrash (229 per 100 with NVP versus 133 per 1000 with EFV; RR 0.58, 95% CI 0.34 to 1.00; 7 trials, 2277 participants; moderate quality evidence). We found that there may be little or no difference in gastrointestinal adverse events (RR 0.76, 95% CI 0.48 to 1.21; 6 trials, 2049 participants; low quality evidence), pyrexia (RR 0.65, 95% CI 0.15 to 2.73; 3 trials, 1799 participants; low quality evidence), raised alkaline phosphatase (RR 0.65, 95% CI 0.17 to 2.50; 1 trial, 1007 participants; low quality evidence), raised amylase (RR 1.40, 95% CI 0.72 to 2.73; 2 trials, 1071 participants; low quality evidence) and raised triglycerides (RR 1.10, 95% CI 0.39 to 3.13; 2 trials, 1071 participants; low quality evidence). There was probably little or no difference in serum glutamic oxaloacetic transaminase (SGOT; MD 3.3, 95% CI -2.06 to 8.66; 1 trial, 135 participants; moderate quality evidence), serum glutamic- pyruvic transaminase (SGPT; MD 5.7, 95% CI -4.23 to 15.63; 1 trial, 135 participants; moderate quality evidence) and raised cholesterol (RR 6.03, 95% CI 0.75 to 48.78; 1 trial, 64 participants; moderate quality evidence).Our subgroup analyses revealed that NVP slightly increases mortality when given once daily (RR 0.34, 95% CI 0.13 to 0.90; 3 trials, 678 participants; high quality evidence). There were little or no differences in the primary outcomes for patients who were concurrently receiving treatment for tuberculosis.
AUTHORS' CONCLUSIONS
Both drugs have similar benefits in initial treatment of HIV infection when combined with two NRTIs. The adverse events encountered affect different systems, with EFV more likely to cause central nervous system adverse events and NVP more likely to raise transaminases, cause neutropenia and rash.
Topics: Adult; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Drug Therapy, Combination; HIV Infections; Humans; Nevirapine; Randomized Controlled Trials as Topic; Reverse Transcriptase Inhibitors; Viral Load
PubMed: 27943261
DOI: 10.1002/14651858.CD004246.pub4 -
International Journal of Surgery... Jun 2019We conducted a systematic review on the diagnostic accuracy of classical and newly reported hematological parameters which are easily available in a resource limited...
BACKGROUND
We conducted a systematic review on the diagnostic accuracy of classical and newly reported hematological parameters which are easily available in a resource limited setting in making a diagnosis of Acute Mesenteric Ischemia (AMI).
METHODS
We searched the PubMed, Scopus, and Cochrane library from January 1940 to April 2018. The search was limited to studies published in English and those involving human subjects only. The diagnostic accuracy of conveniently available parameters: Mean Platelet Volume (MPV), Neutrophil to Lymphocyte Ratio (NLR), Red Cell Distribution Width (RDW), lactate, D-dimer, alkaline aminotransferase, aspartate amino transferase, white blood cell count, lactate dehydrogenase, and amylase were assessed in this review. Studies were only included if they provided sufficient information allowing us to make a diagnostic accuracy contingency table and define a gold standard test. We excluded letters, editorials, and case reports. There were no restrictions to any particular study design. The QUADAS 2 protocol was used for quality appraisal. This study protocol was registered on Prospero with ID CRD42018088953.
RESULTS
Of 560 articles which were initially retrieved, 20 studies, comprising of 2043 participants, were eligible for this review. AMI was diagnosed in 518 patients. D-dimer had the highest median sensitivity of 93% while the median specificity of lactate and NLR were 85.9 and 85.8, respectively.
CONCLUSION
Observing the high heterogeneity among the studies, currently it is difficult to suggest any single marker for diagnosing AMI. Compared to the classical markers, RDW, NLR and MPV showed higher specificities. Using these new markers alongside with the classical markers in the context of a scoring system might help in making a diagnosis of AMI in emergency settings.
Topics: Acute Disease; Aspartate Aminotransferases; Biomarkers; Erythrocyte Indices; Fibrin Fibrinogen Degradation Products; Humans; Leukocyte Count; Lymphocytes; Mean Platelet Volume; Mesenteric Ischemia; Neutrophils; Sensitivity and Specificity
PubMed: 30999055
DOI: 10.1016/j.ijsu.2019.04.005 -
HPB : the Official Journal of the... Jan 2020Early recognition of postoperative pancreatic fistula might decrease the risk of subsequent life threatening complications. The aim of this review was to systematically...
BACKGROUND
Early recognition of postoperative pancreatic fistula might decrease the risk of subsequent life threatening complications. The aim of this review was to systematically evaluate the accuracy of postoperative clinical, biochemical and radiologic variables for early recognition of clinically relevant postoperative pancreatic fistula.
METHODS
A systematic literature search was performed up to August 2018. Clinical studies reporting on the association between postoperative variables and clinically relevant postoperative pancreatic fistula were included. Variables were stratified: early prediction (postoperative day 1-2) versus early diagnosis (day 3) and had to be reported in 2 cohorts.
RESULTS
Overall, 37 included studies reported on 17 different diagnostic variables after 8701 pancreatic resections. Clinically relevant postoperative pancreatic fistula occurred in 1532/8701 patients (18%). Early prediction variables included elevated serum and drain amylase (day 1). Identified variables for early diagnosis were: non-serous drain efflux (day 3); positive drain culture (day 3); elevated temperature (any day); elevated C-Reactive Protein (CRP; day 4); elevated white blood cell count (day 4) and peripancreatic collections on computed tomography (CT; day 5-10).
CONCLUSION
This review provides a comprehensive overview of postoperative variables associated with clinically relevant pancreatic fistula. Incorporation of variables in future algorithms could potentially mitigate the clinical impact of postoperative pancreatic fistula.
Topics: Early Diagnosis; Humans; Pancreatectomy; Pancreatic Fistula; Postoperative Complications; Predictive Value of Tests; Risk Factors
PubMed: 31445782
DOI: 10.1016/j.hpb.2019.07.005 -
International Journal of Molecular... Oct 2020Saliva as a biological fluid has a remarkable potential in the non-invasive diagnostics of several systemic disorders. Inflammatory bowel diseases are chronic...
Saliva as a biological fluid has a remarkable potential in the non-invasive diagnostics of several systemic disorders. Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. This systematic review was designed to answer the question "Are salivary biomarkers reliable for the diagnosis of inflammatory bowel diseases?". Following the inclusion and exclusion criteria, eleven studies were included (according to PRISMA statement guidelines). Due to their heterogeneity, the potential salivary markers for IBD were divided into four groups: oxidative status markers, inflammatory cytokines, microRNAs and other biomarkers. Active CD patients manifest decreased activity of antioxidants (e.g., glutathione, catalase) and increased lipid peroxidation. Therefore, malondialdehyde seems to be a good diagnostic marker of CD. Moreover, elevated concentrations of proinflammatory cytokines (such as interleukin 1β, interleukin 6 or tumour necrosis factor α) are associated with the activity of IBD. Additionaly, selected miRNAs are altered in saliva (overexpressed miR-101 in CD; overexpressed miR-21, miR-31, miR-142-3p and underexpressed miR-142-5p in UC). Among other salivary biomarkers, exosomal PSMA7, α-amylase and calprotectin are detected. In conclusion, saliva contains several biomarkers which can be used credibly for the early diagnosis and regular monitoring of IBD. However, further investigations are necessary to validate these findings, as well as to identify new reliable salivary biomarkers.
Topics: Biomarkers; Cytokines; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; MicroRNAs; Oxidative Stress; Prognosis; Reproducibility of Results; Saliva; Sensitivity and Specificity
PubMed: 33050496
DOI: 10.3390/ijms21207477 -
Nutrients Aug 2020Evidence synthesizing the effects of acute body water losses on various markers of glycemic regulation, appetite, metabolism, and stress is lacking. Thus, the purpose of... (Meta-Analysis)
Meta-Analysis
Evidence synthesizing the effects of acute body water losses on various markers of glycemic regulation, appetite, metabolism, and stress is lacking. Thus, the purpose of this review was to summarize the response of various hormonal changes involved in these physiologic functions to dehydration. A comprehensive literature search for peer-reviewed research in the databases PubMed, Scopus, CINAHL, and SportDiscus was conducted. Studies were included if they contained samples of adults (>18 years) and experimentally induced dehydration as measured by acute body mass loss. Twenty-one articles were eligible for inclusion. Findings suggested cortisol is significantly elevated with hypohydration (standard mean difference [SMD] = 1.12, 95% CI [0.583, 1.67], < 0.0001). Testosterone was significantly lower in studies where hypohydration was accompanied by caloric restriction (SMD= -1.04, 95% CI [-1.93, -0.14], = 0.02), however, there were no changes in testosterone in studies examining hypohydration alone (SMD = -0.17, 95% CI [-0.51 0.16], = 0.30). Insulin and ghrelin were unaffected by acute total body water losses. Acute hypohydration increases markers of catabolism but has a negligible effect on markers of glycemic regulation, appetite, anabolism and stress. Given the brevity of existing research, further research is needed to determine the impact of hydration on glucagon, leptin, peptide YY and the subsequent outcomes relevant to both health and performance.
Topics: Adolescent; Adult; Appetite; Blood Glucose; Caloric Restriction; Dehydration; Female; Ghrelin; Humans; Hydrocortisone; Leptin; Male; Peptide YY; Stress, Physiological; Testosterone; Young Adult; alpha-Amylases
PubMed: 32825404
DOI: 10.3390/nu12092526 -
Digestive Diseases and Sciences May 2021Severe pancreatitis may result in a disrupted pancreatic duct, which is associated with a complicated clinical course. Diagnosis of a disrupted pancreatic duct is not...
BACKGROUND
Severe pancreatitis may result in a disrupted pancreatic duct, which is associated with a complicated clinical course. Diagnosis of a disrupted pancreatic duct is not standardized in clinical practice or international guidelines. We performed a systematic review of the literature on imaging modalities for diagnosing a disrupted pancreatic duct in patients with acute pancreatitis.
METHODS
A systematic search was performed in PubMed, Embase and Cochrane library databases to identify all studies evaluating diagnostic modalities for the diagnosis of a disrupted pancreatic duct in acute pancreatitis. All data regarding diagnostic accuracy were extracted.
RESULTS
We included 8 studies, evaluating five different diagnostic modalities in 142 patients with severe acute pancreatitis. Study quality was assessed, with proportionally divided high and low risk of bias and low applicability concerns in 75% of the studies. A sensitivity of 100% was reported for endoscopic ultrasound and endoscopic retrograde cholangiopancreatography. The sensitivity of magnetic resonance cholangiopancreatography with or without secretin was 83%. A sensitivity of 92% was demonstrated for a combined cohort of secretin-magnetic resonance cholangiopancreatography and magnetic resonance cholangiopancreatography. A sensitivity of 100% and specificity of 50% was found for amylase measurements in drain fluid compared with ERCP.
CONCLUSIONS
This review suggests that various diagnostic modalities are accurate in diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. Amylase measurement in drain fluid should be standardized. Given the invasive nature of other modalities, secretin-magnetic resonance cholangiopancreatography or magnetic resonance cholangiopancreatography would be recommended as first diagnostic modality. Further prospective studies, however, are needed.
Topics: Amylases; Biomarkers; Cholangiopancreatography, Endoscopic Retrograde; Cholangiopancreatography, Magnetic Resonance; Clinical Enzyme Tests; Endosonography; Humans; Pancreatic Ducts; Pancreatitis; Predictive Value of Tests; Reproducibility of Results; Secretin; Severity of Illness Index
PubMed: 32594462
DOI: 10.1007/s10620-020-06413-0 -
Journal of Clinical Laboratory Analysis Dec 2020A common problem in clinical laboratories is maintaining the stability of analytes during pre-analytical processes. The aim of this study was to systematically summarize...
OBJECTIVE
A common problem in clinical laboratories is maintaining the stability of analytes during pre-analytical processes. The aim of this study was to systematically summarize the results of a set of studies about the biochemical analytes stability.
METHODS
A literature search was performed on the Advanced search field of PubMed using the keywords: "(stability) AND (analytes OR laboratory analytes OR laboratory tests OR biochemical analytes OR biochemical tests OR biochemical laboratory tests)." A total of 56 entries were obtained. After applying the selection criteria, 20 articles were included in the study.
RESULTS
In the 20 included references, up to 123 different analytes were assessed. The 34 analytes in order of the most frequently studied analytes were evaluated: Alanine aminotransferase, aspartate aminotransferase, potassium, triglyceride, alkaline phosphatase, creatinine, total cholesterol, albumin, lactate dehydrogenase, sodium, calcium, γ-glutamyltransferase, total bilirubin, urea, creatine kinase, inorganic phosphate, total protein, uric acid, amylase, chloride, high-density lipoprotein, magnesium, glucose, C-reactive protein, bicarbonate, ferritin, iron, lipase, transferrin, cobalamin, cortisol, folate, free thyroxine, and thyroid-stimulating hormone. Stable test results could be varied between 2 hours and 1 week according to the type of samples and/or type of blood collection tubes on a basic classification set as refrigerated or room temperature.
CONCLUSIONS
Biochemical analytes stability could be improved if the best pre-analytical approaches are used.
Topics: Biomarkers; Blood Chemical Analysis; Blood Specimen Collection; Humans; Sample Size; Time Factors
PubMed: 32869910
DOI: 10.1002/jcla.23551 -
Virchows Archiv : An International... Jul 2021Cystic lesions of the pancreas may range from benign to precursors of pancreatic cancer. Simple mucinous cyst (SMC) is larger than 1 cm, has a gastric-type flat mucinous...
Cystic lesions of the pancreas may range from benign to precursors of pancreatic cancer. Simple mucinous cyst (SMC) is larger than 1 cm, has a gastric-type flat mucinous lining, and minimal atypia without ovarian-type stroma. We report a new case of pancreatic SMC, coupling a systematic review of the English literature mainly focused on their clinic-pathological features. We reviewed 103 cases of SMC in adults (73 women), averaging 57 (range, 26-70) years. The SMCs were located in the body-tail region of the pancreas in 60 (58%) cases, presenting as single cystic lesions in 94% of cases; 43% of patients were asymptomatic. A preoperative fine-needle aspiration of the cyst fluid detected amylase and carcinoembryonic antigen positivity in 71% and 76% of cases, respectively. Patients underwent surgery mostly for suspected malignancy; in 83% of cases, a standard pancreatic resection was performed. Mean SMC size was 4.9 (range, 1.5-12.0) cm. Mucins MUC5AC and MUC6 resulted positive in 77% and 81% of cases performed, respectively, whereas MUC2 was negative in all but one patient. The SMC from our institution was characterized by a KRAS somatic mutation. The diagnosis of SMC should be considered when a solitary pancreatic cyst larger than 1 cm is detected in asymptomatic patients. To establish a correct diagnosis, an extensive histologic/immunohistochemical analysis is essential. The presence of a KRAS mutation highlights that SMC may represent another potential pancreatic cancer precursor.
Topics: Adult; Aged; Amylases; Biomarkers, Tumor; Carcinoembryonic Antigen; Cystadenoma, Mucinous; Female; Humans; Male; Middle Aged; Mucin 5AC; Mucin-6; Mutation; Pancreatectomy; Pancreatic Cyst; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Precancerous Conditions; Proto-Oncogene Proteins p21(ras)
PubMed: 33511431
DOI: 10.1007/s00428-021-03029-1