Placebo-controlled efficacy of 5-HT3 antagonists for postoperative nausea and vomiting prophylaxis in supratentorial craniotomies: A systematic review and comparative meta-analysis of randomized clinical trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are common and distressing complications following neurosurgical procedures, affecting up to 73 % of patients undergoing craniotomy. Therefore, we aimed to assess the placebo-controlled efficacy of 5-HT3 antagonists to prevent PONV following supratentorial craniotomies. METHODS: We searched Medline, Web of Science, and Embase databases following PRISMA guidelines for RCTs comparing the outcomes of prophylactic use of 5-HT3 antagonists with placebo to prevent PONV following supratentorial craniotomy. We pooled odds ratios (OR) with 95 % confidence intervals with a random-effects model. I2 statistics was used to assess heterogeneity. RESULTS: Five RCTs, comprising 347 patients, of which 145 received a placebo, were included. The analysis identified a lower likelihood of early postoperative vomiting in 5-HT3 antagonists group (OR=0.47; 95 % CI: 0.24-0.91, p<0.05; I2=7 %), a lower likelihood of vomit within the 24-h period in 5-HT3 antagonists group (OR=0.27; 95 % CI: 0.15-0.48, p<0.01; I2=40 %), a lower likelihood of nausea within the 24-h period in 5-HT3 antagonists group (OR=0.47; 95 % CI: 0.28-0.72, p<0.01; I2=34 %), and a lower likelihood of rescue interventions in 5-HT3 antagonists group (OR = 0.18; 95 % CI: 0.10-0.34; I2 = 0 %. Subgroup analyses focusing on ondansetron also identified a lower likelihood of nausea and vomiting within the 24-h period in the 5-HT3 antagonist group. CONCLUSION: This systematic review and meta-analysis identified that 5-HT3 antagonists are effective in preventing PONV in the postoperative period following supratentorial craniotomy when compared to placebo. Our findings provide synthesized and robust evidence derived from randomized studies to support the use of 5-HT3 antagonists in clinical practice.

Challenges and limitations in meta-analyses of complications in neurosurgery: Systematic review with proposed approach and checklist to mitigate errors and improve the assessment of the real-world experience.

Meta-analyses are highly valued in medical science, yet accurately reporting complications in neurosurgical studies remains challenging. Examples include inconsistencies in defining and classifying complications and variations in reporting methods. This lack of reproducibility and comparability, along with other issues related to biases, hinders the ability of meta-analyses to yield significant advancements. This systematic review investigated the challenges and limitations inherent in meta-analyses of complications in neurosurgery. Based on the identified challenges and our group's experience, we developed a practical checklist to mitigate and avoid common errors in meta-analyses of complications in neurosurgery.We searched PubMed, Embase, and Web of Science for studies addressing challenges in assessing complications in neurosurgery. The main findings were qualitatively synthesized to identify common challenges and limitations. The proposed checklist was developed using a modified Delphi technique. Eleven studies were included, uncovering heterogeneity and a lack of standardization regarding the classification of complications in neurosurgery across various authors and institutions. They suggested solutions such as implementing a more uniform classification system. Additionally, the NeuroComp Meta-Analysis Checklist was developed, comprising 23 items divided into 5 domains, with a practical approach and suggestions on how to deal with the challenges when meta-analyzing.We identified numerous challenges and concerns when assessing complications in the neurosurgical field. The NeuroComp Meta-Analysis Checklist incorporated methodologies and approaches we utilized in several previously published meta-analyses. While we acknowledge that the proposal cannot solve all the issues involved in comparing and meta-analyzing complications in neurosurgery, it has the potential to enhance the informativeness of future meta-analyses and help authors mitigate common errors. Ultimately, this tool has the potential to contribute to the advancement of accumulating real-world evidence in neurosurgical science.

Anti-GABAB Receptor Autoimmune Encephalitis: A Report of a Rare Case in Central America.

Autoimmune encephalitis (AE) is a rare disease. There have been very few reports of anti-GABAB receptor encephalitis, and no case of this subtype has ever been reported in Central America. We present a case of a 21-year-old male patient with an unremarkable previous medical history who was hospitalized because of a new onset of seizures and status epilepticus. Central nervous system infections, neoplastic disorders, cerebrovascular disease, septic and metabolic encephalopathy, and drug toxicity were ruled out. Cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis and oligoclonal bands. Initial head computed tomography (CT) scans with and without contrast were normal, and brain magnetic resonance imaging (MRI) showed no abnormalities. An electroencephalogram showed slow waves and spike waves in the frontal and temporal areas. During hospitalization, encephalopathy progressed, along with seizures and altered mental status requiring mechanical ventilation and admission to the intensive care unit. Intravenous valproic acid and phenytoin for seizure control were given. The unexplained seizures, persisting altered mental status despite the reduction of sedatives, CSF pleocytosis, and oligoclonal bands, along with reasonable exclusion of alternative disorders, suggested AE. The diagnosis was confirmed with positive anti-GABAB1-B2 receptor antibody titers in serum and CSF. A whole-body CT scan showed increased pancreatic head size, but endoscopic ultrasonography ruled out malignancy, and a normal IgG4 range excluded IgG4 disease. The patient received treatment with methylprednisolone, plasmapheresis, and immunoglobulin therapy, with excellent response. The patient has been followed up for seven months, taking immunomodulation with mycophenolate. He is seizure-free with valproic acid and levetiracetam treatment and is receiving cognitive rehabilitation after mild cognitive decline was noted in the psychometric analysis.

Spontaneous Cushing's Disease Remission Induced by Pituitary Apoplexy.

Spontaneous remission of Cushing's disease (CD) is uncommon and often attributed to pituitary tumor apoplexy. We present a case involving a 14-year-old female who exhibited clinical features of Cushing's syndrome. Initial diagnostic tests indicated CD: elevated 24h urinary cortisol (235 µg/24h, n < 90 µg/24h), abnormal 1 mg dexamethasone overnight test (cortisol after 1 mg dex 3.4 µg/dL, n < 1.8 µg/dL), and elevated adrenocorticotropic hormone concentrations (83.5 pg/mL, n 10-60 pg/mL). A pituitary adenoma was suspected, so a nuclear MRI was performed, with findings suggestive of a pituitary microadenoma. The patient was referred for a transsphenoidal resection of the microadenoma. While waiting for surgery, the patient presented to the emergency department with a headache and clinical signs of meningism. A computed axial tomography of the central nervous system was performed, and no structural alterations were found. The symptoms subsided with analgesia. One month later, she presented again to the emergency department with clinical findings of acute adrenal insufficiency (cortisol level of 4.06 µg/dL), and she was noted to have spontaneous biochemical remission associated with the resolution of her symptoms of hypercortisolism. For that reason, spontaneous CD remission induced by pituitary apoplexy (PA) was diagnosed. The patient has been managed conservatively since the diagnosis and remains in clinical and biochemical remission until the present time, after 10 months of follow-up. There are three unique aspects of our case: the early age of onset of symptoms, the spontaneous remission of CD due to PA, which has been rarely reported in the medical literature, and the fact that the patient presented a microadenoma because there are fewer than 10 clinical case reports of PA associated with microadenoma.

Adrenocorticotropic Hormone Producing Pituitary Carcinoma in the Falx Cerebri, Retroclival Region, Ethmoidal Cells, and Other Locations.

Pituitary carcinoma is a condition defined by metastasis of a pituitary tumor to a distant location, and it is a very rare type of adenohypophyseal tumor. We present a case of a 29-year-old female who was followed up in our Endocrinology Department. Past medical history included the diagnosis of Cushing disease and transsphenoidal tumor resection at 12 years of age, followed by transcranial resection two years later because of persistently elevated adrenocorticotropic hormone (ACTH). Despite the surgical management, the patient persisted with increased ACTH and hypercortisolism, and, thus, bilateral adrenalectomy was performed a year later. Two years after the procedure, the patient presented with a newly diagnosed pituitary macroadenoma, and the diagnosis of Nelson syndrome was made. Linear accelerator radiotherapy was given, which reduced the size of the tumor. Later, several imaging studies showed multiple lesions on the falx cerebri, posterior clinoid process, retroclival region, cerebellopontine angle, pterygopalatine fossa, infratentorial region, and posterior ethmoidal cells. Biopsy and immunohistochemistry of the falx cerebri lesions described ACTH-producing pituitary adenocarcinoma. Treatment was given with intramuscular octreotide, dabrafenib, and trametinib. Despite persistently elevated ACTH levels, the patient has since remained clinically stable, without new development or worsening of symptoms. There are three unique aspects of our case. First, we reported an unusual presentation of this disease, since the patient in our case was a female with an early age of onset. Second, this is the first reported case demonstrating pituitary carcinoma in the falx cerebri. Third, the prognosis of pituitary carcinoma is usually very poor, and mortality is extremely high; however, the patient in our case has been followed up for seven years since the diagnosis of the metastatic lesions and has remained clinically stable.

Comparative efficacy and safety of sodium fluorescein-guided surgery versus standard white light for resection of brain metastases: a systematic review and meta-analysis.

PURPOSE: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs. METHODS: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity. RESULTS: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions. CONCLUSION: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs.

Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities.

Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking. Use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD. As a result, confusion exists among medical professionals about the appropriate management of people with gout and CKD. This Consensus Statement from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) discusses the evidence and/or lack thereof for the management of gout in people with CKD and identifies key areas for research to address the challenges faced in the management of gout and CKD. These discussions, which address areas for research both in general as well as related to specific medications used to treat gout flares or as ULT, are supported by separately published G-CAN systematic literature reviews. This Consensus Statement is not intended as a guideline for the management of gout in CKD; rather, it analyses the available literature on the safety and efficacy of drugs used in gout management to identify important gaps in knowledge and associated areas for research.

Efficacy and safety of urate-lowering therapy in people with kidney impairment: a GCAN-initiated literature review.

OBJECTIVES: The aim was to evaluate the efficacy, defined as achieving target serum urate <6.0 mg/dl, and safety of urate-lowering therapies (ULTs) for people with gout and chronic kidney disease (CKD) stages 3-5. METHODS: PubMed, The Cochrane Library and EMBASE were searched from 1 January 1959 to 31 January 2018 for studies that enrolled people with gout, who had an estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) of <60 ml/min and exposure to allopurinol, febuxostat, probenecid, benzbromarone, lesinurad or pegloticase. All study designs other than case reports were included, except for people on dialysis, for whom we did include case reports. RESULTS: There were 36 reports with an analysis of efficacy and/or safety based upon renal function: allopurinol (n = 12), febuxostat (n = 10), probenecid (n = 3), benzbromarone (n = 5), lesinurad (n = 5) and pegloticase (n = 1). There were 108 reports that involved people with gout and renal impairment but did not contain any analysis on efficacy and/or safety based upon renal function: allopurinol (n = 84), febuxostat (n = 14), benzbromarone (n = 1), lesinurad (n = 3) and pegloticase (n = 6). Most studies excluded people with more severe degrees of renal impairment (eGFR or CrCl of <30 ml/min). For allopurinol, in particular, there was significant variability in the dose of drug used and the efficacy in terms of urate lowering, across all levels of renal impairment. CONCLUSION: There is a lack of evidence regarding the efficacy and/or safety of currently used ULTs according to different levels of renal function. Future studies should include patients with CKD and should report study outcomes stratified by renal function.

Flare Rate Thresholds for Patient Assessment of Disease Activity States in Gout.

OBJECTIVE: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS). METHODS: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state. RESULTS: Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively. CONCLUSION: Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity.

High Levels of Polypharmacy in Rheumatoid Arthritis-A Challenge Not Covered by Current Management Recommendations: Data From a Large Real-Life Study.

BACKGROUND: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis. OBJECTIVE: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting. METHODS: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression. RESULTS: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs). CONCLUSION: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.

Trypanosoma brucei triggers a marked immune response in male reproductive organs.

African trypanosomiasis is caused by the protozoan parasite Trypanosoma brucei, transmitted between mammals by the bite of a tsetse. It has been recently shown that parasites accumulate in large numbers in various organs and tissues, including the mouse testis. Whether parasites are protected from the immune system in the male reproductive organ or can be transmitted through sexual route remains unknown. Here we show that parasites can be detected by fine needle aspiration cytology of the male reproductive system in mice, and histopathological analysis revealed that T. brucei accumulates in the stroma of the epididymis, epididymal adipose tissue and fibrous tunics of the testis. No parasites were found in the lumen of intact epididymal ducts or seminiferous tubules of the testis, indicating that the large majority of the parasites are not located in immune-privileged sites. In fact, these parasites are associated with marked inflammatory cell infiltration, parasite degeneration, and severe tissue damage and rupture of epididymal ducts, which may be related with reduced fertility. Overall, we show that just like in the bloodstream and most other tissues, in the male reproductive organs, T. brucei are exposed to a strong immune response. The detection of a very high number of parasites in this organ and its accessibility opens the possibility of using fine needle aspiration cytology as a complementary diagnostic tool in Animal African Trypanosomiasis.

Patterns of land use, extensification, and intensification of Brazilian agriculture.

Sustainable intensification of agriculture is one of the main strategies to provide global food security. However, its implementation raises enormous political, technological, and social challenges. Meeting these challenges will require, among other things, accurate information on the spatial and temporal patterns of agricultural land use and yield. Here, we investigate historical patterns of agricultural land use (1940-2012) and productivity (1990-2012) in Brazil using a new high-resolution (approximately 1 km(2) ) spatially explicit reconstruction. Although Brazilian agriculture has been historically known for its extensification over natural vegetation (Amazon and Cerrado), data from recent years indicate that extensification has slowed down and was replaced by a strong trend of intensification. Our results provide the first comprehensive historical overview of agricultural land use and productivity in Brazil, providing clear insights to guide future territorial planning, sustainable agriculture, policy, and decision-making.

Pregnancy outcome in juvenile systemic lupus erythematosus: a Brazilian multicenter cohort study.

OBJECTIVE: To determine pregnancy outcome and fetal loss risk factors in patients with juvenile systemic lupus erythematosus (JSLE). METHODS: A total of 315 female patients with JSLE followed in 12 Brazilian pediatric rheumatology centers were consecutively selected. Menarche was observed in 298 (94.6%) patients. Patients' medical records were reviewed for pregnancy outcomes and demographic, clinical, and therapeutic data. RESULTS: A total of 24 unplanned pregnancies occurred in 298 (8%) patients. The outcomes were 5 (21%) early fetal losses (prior to 16 wks gestation), 18 (75%) live births, and 1 (4%) death due to preeclampsia and premature birth. The frequencies of active diffuse proliferative glomerulonephritis, proteinuria > or = 0.5 g/day, and arterial hypertension at the beginning of pregnancy were higher in pregnancies resulting in fetal losses than in live births [60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), respectively]. JSLE pregnancies with fetal losses had a significantly higher mean SLE Disease Activity Index 2000 (SLEDAI-2K) at the start of pregnancy compared with those with live births (9.40 +/- 7.47 vs 3.94 +/- 6.00; p = 0.049). Four pregnancies were inadvertently exposed to intravenous cyclophosphamide therapy for renal involvement despite contraceptive prescriptions, resulting in fetal loss in 3 (p = 0.02). In multivariate analysis only intravenous cyclophosphamide use at start of pregnancy (OR 25.50, 95% CI 1.72-377.93, p = 0.019) remained as an independent risk factor for fetal loss. CONCLUSION: We identified immunosuppressive therapy as the major contributing factor for fetal loss in JSLE, reinforcing the importance of contraception.