Good clinical outcomes and the necessity of CSF drainage in patients undergoing simultaneous biopsy and endoscopic third ventriculostomy in the region of pineal tumors: A systematic review and meta-analysis.

INTRODUCTION: Due to their delicate and deep-seated location, tumors in the pineal region of the brain pose exceptional challenges in neurosurgical management. Highly precise procedures have become crucial to address these complexities, such as the simultaneous performance of biopsy and endoscopic third ventriculostomy (ETV). Our aim was to assess the feasibility, safety, and efficacy of simultaneous biopsy and ETV for treating patients with pineal region tumors. METHODS: Medline, Embase, and Web of Science were searched for English studies from January 2000 to February 2024, following Cochrane and PRISMA guidelines. Eligible studies encompassed a minimum of four patients and examined at least one of the following outcomes: good clinical outcomes and the necessity of shunt placement. Single proportion analysis with 95% confidence intervals was conducted under a random-effects model, employing the I2 statistic to assess heterogeneity. Additionally, publication bias was evaluated using the ROBINS-I tool. RESULTS: After a meticulous selection process, eighteen studies involving 390 patients were included in the analysis. Overall, good clinical outcomes were observed in 131 out of 147 patients, representing a rate of 92 % (95 % CI: 84 % to 100 %, I2 = 62 %) through random effects analysis. Subgroup analysis showed that children exhibited a notably high rate of good clinical outcomes, reaching 100 % (95 % CI: 96 % to 100 %, I2 = 0 %). Regarding the need for shunt placement, out of the 356 patients assessed, only 39 required shunt placement, yielding a rate of 8 % (95 % CI: 4 % to 12 %, I2 = 63 %). Further sub-analyses indicated shunt requirement rates of 12 % for children and 3 % for adults. Specifically focusing on adults, data from 46 patients who underwent biopsy revealed a success rate of 84 % (95 % CI: 62 % to 100 %, I2 = 81 %). Remarkably, no major complications were reported among adults, resulting in a rate of 0 % (95 % CI: 0 % to 6 %, I2 = 0 %). Additionally, low rates of mortality related to the procedure were observed in adults, with two deaths recorded among the 46 patients analyzed, resulting in a mortality rate of 1 % (95 % CI: 0 % to 7 %, I2 = 0 %). CONCLUSION: In conclusion, our study aimed to assess the feasibility, safety, and efficacy of performing simultaneous biopsy and ETV for patients with pineal region tumors. We meticulously examined clinical aspects and patient outcomes, including good clinical outcomes, the requirement for shunt placement after ETV, biopsy success rates, mortality, and complications.

Are ventriculopleural shunts the second option for treating hydrocephalus? A meta-analysis of 543 patients.

BACKGROUND: Some centers utilize ventriculopleural shunt (VPLS) for treating hydrocephalus when conventional approaches are not feasible. Nonetheless, the literature regarding this approach is scarce. PURPOSE: Evaluate the outcomes of VPLS through a single-arm meta-analysis. METHODS: Following PRISMA guidelines, the authors systematically searched for articles utilizing the VPLS in a cohort with more than four patients. Outcomes included: mortality, pleural effusion, number of patients who underwent revisions, obstructions, shunt migration, emphysema, and subdural hematoma. RESULTS: A total of 404 articles were reviewed, resulting in the inclusion of 13 retrospective studies encompassing 543 patients, with the majority being children (62.6 %). The median average follow-up period was 35.4 months (10-64.1). After analysis, results yielded a revision rate of 54 % (95 % CI: 44 %-64 %; I2=73 %). The most common complication observed was pleural effusion, with a post-analysis incidence of 16 % (95 % CI: 11 %-21 %; I2=63 %), followed by infections at 7 % (95 % CI: 4 %-10 %; I2=33 %). Shunt obstruction occurred in 13 % (95 % CI: 4 %-21 %; I2=84 %) of cases after analysis, while migrations, overdrainage, subdural hematoma, and cutaneous emphysema had minimal occurrence rates (0 %, 95 % CI: 0 %-1 %; I2=0 %). Notably, there were no reported cases of shunt-related mortality. CONCLUSION: VPLS can be considered when there are no other suitable options for placing the distal catheter. However, the notable rates of shunt revisions, pleural effusion, infections, and the inherent heterogeneity of outcomes currently limit the widespread adoption of VPLS. In this scenario, other alternatives should be given priority.

Extramedullary Intracranial Plasmacytomas: A Systematic Review of Literature.

Extramedullary plasmacytoma (EMP) is an uncommon disorder characterized by the development of abnormal plasma cell tumors outside the bone marrow. These tumors are typically observed in various locations, including the upper respiratory tract, gastrointestinal tract, and other soft tissues. Among the less explored manifestations of EMP is intracranial EMP, which remains poorly understood due to the limited literature available on the subject. The objective was to comprehend the population characteristics, localization, type, treatment, and outcomes of intracranial EMP. A systematic review of the literature for EMPs was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The strategy "extramedullary plasmacytoma AND multiple myeloma" was used for the search. The search terms were queried using PubMed, Embase, Scopus, Cochrane, and Web of Science databases. We included only those studies that presented clinical studies with patients diagnosed with intracranial plasmacytomas. In this study, a total of 84 patients from 25 studies were analyzed. The average age of diagnosis was 57.25 years, with a slightly higher proportion of females (57%) compared to male patients (43%). The most common locations of intracranial plasmacytomas were the clivus (29.7%), frontal lobe (18.9%), parietal lobe (8.1%), occipital lobe (6.7%), temporal lobe (6.7%), and sphenoid (4%). Chordoma and meningioma were the most common differential diagnoses encountered during clinical investigations. Treatment modalities included radiotherapy (RT), chemotherapy (QT), surgical resection (SR), and conservative approaches. The most frequent treatment combinations were SR + RT (19%) and RT only (17.8%). Mortality was reported in 48% of the cases, with complete resolution observed in 10 cases and partial resolution in 3 cases. The average follow-up duration was 37.5 months. The clivus is the most frequently reported site of extramedullary intracranial plasmacytoma (EMIP) occurrence, representing 29.7% of cases. Chordomas were commonly observed alongside EMIPs and emerged as the primary differential diagnosis. RT was the predominant treatment modality, with SR considered when feasible. RT alone demonstrated the highest effectiveness in managing EMIPs (30%), while QT as a sole intervention showed lower efficacy. However, a combination of dexamethasone, lenalidomide, and targeted RT displayed promising results, offering improved tumor response and increased safety.

Adenosine-assisted embolization of cerebral arteriovenous malformations: a systematic review and meta-analysis.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are complex lesions that can cause hemorrhagic stroke and significant neurological disability. Adenosine induces cardiac standstill and hypotension, which are thought to be useful during cerebral AVM embolization. Herein, we conducted a systematic review and meta-analysis of the technique's safety. METHODS: Following PRISMA guidelines, four databases were queried for studies describing the use of adenosine-assisted embolization of cerebral AVMs. Adenosine-related intraoperative complications, permanent neurological outcomes, morbidity, and mortality assessed the technique's safety. Single proportion analysis under a random-effects model was performed. Heterogeneity was assessed using I² statistics, and publication bias was evaluated through funnel plot analysis and Egger's regression test. RESULTS: Ten studies were included, involving 79 patients (55.7% male) with 79 AVMs (54.4% unruptured and 70.9% Spetzler-Martin grade III-V) who underwent 123 embolizations (80.4% and 5.9% under transarterial and transvenous approaches, respectively) with n-butyl cyanoacrylate (80.4%), ethylene vinyl alcohol (14.4%), or both (5.2%). The incidence of transient adenosine-related intraoperative complications was 0% (95% CI 0% to 3%, I2=24%). Besides, the incidence of adenosine-related morbidity, mortality, and permanent outcomes was 0% (95% CI 0% to 3%, I2=0%). During follow-up, good functional outcomes were reported for 64 patients (81%). CONCLUSIONS: Adenosine's effects on blood flow control can facilitate embolization and mitigate the risk of AVM rupture and embolic agent migration. Although current evidence stems from observational studies, the results of this meta-analysis suggest a safe drug profile due to minimal associated morbidity and mortality. Further research from larger randomized and controlled studies is warranted to attain a higher level of evidence. PROSPERO REGISTRY NUMBER: CRD42023494116.

When microsurgery becomes the only lifesaving resource: An institutional experience treating patients from low-income backgrounds affected by posterior circulation brain aneurysms.

BACKGROUND AND OBJECTIVE: Aneurysms of the posterior cerebral circulation constitute a burdensome condition with high mortality and morbidity. In the modern era, there has been a trend toward favoring an endovascular approach over microsurgery for aneurysm cases. Nevertheless, this transition has yet to be mirrored in low-to-middle-income countries where endovascular therapy may not be widely available. Herein, we aim to illustrate our experience treating these challenging conditions in patients from low-income backgrounds and discuss the relevance of the clinical setting in the treatment decision. METHODS: The authors conducted a retrospective review of the health records of patients who received microsurgical treatment for aneurysms in the posterior circulation, including the basilar artery (BA), posterior cerebral artery (PCA), and posterior inferior cerebellar artery (PICA) in an institution providing treatment to people of low-income backgrounds. Epidemiological data, microsurgical technique, and neurological function were retrieved and analyzed. RESULTS: Surgical clipping was employed for 12 patients (75% female) harboring 15 aneurysms (87% in the posterior circulation and 62% ruptured at presentation). Aneurysms were predominately located in the BA (69%), followed by the PCA (15%) and PICA (15%). Among neurological complications, 25% of patients developed oculomotor nerve palsy. The mortality rate was 17% owing to complications such as cerebral vasospasm, infarction, and severe intracranial hypertension. At the 6-month follow-up, 90% of patients had a good clinical outcome (modified Rankin scale scores of 0-2). CONCLUSION: The present case series illustrates the manifest role of microsurgical techniques for posterior circulation aneurysms, particularly in a scenario where endovascular techniques are not easily accessible. Importantly, this clinical setting pressure could exhort trainees to strive for microsurgical mastery and gain a competitive advantage.

Same-day discharge in craniotomy: A systematic review and meta-analysis.

BACKGROUND: Traditionally, patients undergoing craniotomy were subject to extended hospital stays for intensive monitoring and management of potential complications. However, with the evolution of surgical methods, anesthesia, and postoperative protocols, the feasibility and interest in same-day discharge (SDD) are growing. This study aimed to evaluate whether same-day discharge is a safe and feasible approach in craniotomy through a meta-analysis of the available literature. METHODS: Following PRISMA guidelines, a comprehensive search was conducted across Medline, Embase, Cochrane, and Web of Science databases from inception to December 2023. Eligible studies comprised reports in English with a minimum of 4 patients who underwent craniotomies and were discharged with same-day discharge, whether single-arm or comparative with normal discharge. Single proportion analysis with 95 % confidence interval (CI) was used to pool the studies and Odds Ratio (OR) with 95 % CI was used to measure effects in comparative analysis. A random-effects model was adopted. Endpoints included success and failure of pre-planned same-day discharge, and postoperative complications throughout the hospital stay (until discharge), these complications were further categorized into major and minor complications. Also, need for reoperation, readmission within 24 h, readmission after 24 h, and mortality. RESULTS: Seven observational studies were included. Five studies were included in the single-arm analysis, comprising data from 715 patients. Four studies comprising 731 patients were included in the comparative analysis, of whom 233 were discharged on SDD, and 498 were discharged normally. The analysis revealed a success rate of 88 % (95 % CI, 83 %-94 %), readmission to the hospital within the initial 24 h rate of 2 % (95 % CI, 1 %-2 %), readmission after 24 h rate of 1 % (95 % CI, 0 %-2 %;), total postoperative complications until discharge rate of 2 % (95 % CI, 1 %-4 %), major complications rate of 0 % (95 % CI, 0 %-0 %), minor complications rate of 2 % (95 % CI, 1 %-4 %), and mortality rate of 0 % (95 % CI, 0 %-0 %). Comparative analysis for complications and mortality showed no difference between both approaches. CONCLUSION: This systematic review and meta-analysis identified that same-day discharge in craniotomy for selected patients, as well as for tumor resection craniotomies, is highly feasible and safe, with a high success rate, low failure, and reoperation rates. Moreover, for selected patients, no evidence of harm in same-day discharge was identified when compared with normal discharge. Consequently, same-day discharge may be considered a viable option, provided appropriate selection criteria are employed.

Optimizing radiotherapy strategies for skull base chordoma: a comprehensive meta-analysis and systematic review of treatment modalities and outcomes.

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. METHODS: Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05. RESULTS: A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively. CONCLUSIONS: The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

Efficacy and safety of microvascular decompression with or without partial sensory rhizotomy: a comprehensive meta-analysis and systematic review in treating trigeminal neuralgia.

Classical trigeminal neuralgia (TN), caused by vascular compression of the nerve root, is a severe cause of pain with a considerable impact on a patient's quality of life. While microvascular decompression (MVD) has lower recurrence rates when compared with partial sensory rhizotomy (PSR) alone, refractoriness can still be as high as 47%. We aimed to assess the efficacy and safety profile of MVD + PSR when compared to standalone MVD for TN. We searched Medline, Embase, and Web of Science following PRISMA guidelines. Eligible studies included those with ≥ 4 patients, in English, published between January 1980 and December 2023, comparing MVD vs. MVD + PSR for TN. Endpoints were pain cure, immediate post-operative pain improvement, long-term effectiveness, long-term recurrence, and complications (facial numbness, hearing loss, and intracranial bleeding). We pooled odds ratios (OR) with 95% confidence intervals with a random-effects model. I2 was used to assess heterogeneity, and sensitivity and Baujat analysis were conducted to address high heterogeneity. Eight studies were included, comprising a total of 1,338 patients, of whom 1,011 were treated with MVD and 327 with MVD + PSR. Pain cure analysis revealed a lower likelihood of pain cure in patients treated with MVD when compared to patients treated with MVD + PSR (OR = 0.30, 95% CI: 0.13 to 0.72). Immediate postoperative pain improvement assessment revealed a lower likelihood of improvement in the MVD group when compared with the MVD + PSR group (OR = 0.31, 95% CI: 0.10 to 0.95). Facial numbness assessment revealed a lower likelihood of occurrence in MVD alone when compared to MVD + PSR (OR = 0.08, 95% CI: 0.04 to 0.15). Long-term effectiveness, long-term recurrence, hearing loss, and intracranial bleeding analyses revealed no difference between both approaches. Our meta-analysis identified that MVD + PSR was superior to MVD for pain cure and immediate postoperative pain improvement for treating TN. However, MVD + PSR demonstrated a higher likelihood of facial numbness complications. Furthermore, identified that hearing loss and intracranial bleeding complications appear comparable between the two treatments, and no difference between long-term effectiveness and recurrence.

Clinical and Technical Outcomes of Intracranial-Intracranial Bypass for Treating Complex Intracranial Aneurysms: An Analysis of 255 Patients.

BACKGROUND: Despite the recent increase in publications centered on intracranial-intracranial (IC-IC) bypasses for complex aneurysms, there is no systematic evidence regarding their outcomes. The purpose was to assess the outcomes of patients subjected to IC-IC bypass for aneurysms. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, a systematic review was conducted. Criteria for inclusion entailed studies with a cohort of at least 4 patients having undergone IC-IC bypass for aneurysms, detailing at least one outcome, such as patency, clinical outcomes, complications, and procedure-related mortality. When the study included patients who had undergone extracranial-intracranial (EC-IC) bypass, the authors extracted the patency and clinical data to juxtapose them with the results of IC-IC. RESULTS: Of the 2509 shortlisted studies, 22 met our inclusion criteria, encompassing 255 patients and 263 IC-IC bypass procedures. The IC-IC bypass procedure exhibited a patency rate of 93% (95% confidence interval [CI]: 89%-95%). The patency rate of IC-IC and EC-IC bypasses did not significantly differ (odds ratio=0.60 [95% CI: 0.18-1.96]). Concerning clinical outcomes, 91% of the IC-IC patients had positive results (95% CI: 85%-97%), with no significant disparity between the IC-IC and EC-IC groups (odds ratio=1.29 [95% CI: 0.43-3.88]). After analysis, the complication rate was 11% (95% CI: 5%-18%). Procedure-related mortality was 1% (95% CI: 0%-4%). CONCLUSIONS: IC-IC bypass is valuable for the treatment of complex intracranial aneurysms, boasting high patency and positive clinical outcomes. Complications are unusual, and procedure-related mortality is minimal. Comparing IC-IC and EC-IC led to no significant differences.

Nonlinear hydrological time series modeling to forecast river level dynamics in the Rio Negro Uruguay basin.

Floods significantly impact the well-being and development of communities. Hence, understanding their causes and establishing methodologies for risk prevention is a critical challenge for effective warning systems. Complex systems such as hydrological basins are modeled through hydrological models that have been utilized to understand water recharge of aquifers, available volume of dams, and floods in diverse regions. Acquiring real-time hydrometeorological data from basins and rivers is vital for establishing data-driven-based models as tools for the prediction of river-level dynamics and for understanding its nonlinear behavior. This paper introduces a hydrological model based on a multilayer perceptron neural network as a useful tool for time series modeling and forecasting river levels in three stations of the Rio Negro basin in Uruguay. Daily time series of river levels and rainfall serve as the input data for the model. The assessment of the models is based on metrics such as the Nash-Sutcliffe coefficient, the root mean square error, percent bias, and volumetric efficiency. The outputs exhibit varying model performance and accuracy during the prediction period across different sub-basin scales, revealing the neural network's ability to learn river dynamics. Lagged time series analysis demonstrates the potential for chaos in river-level time series over extended time periods, mainly when predicting dam-related scenarios, which shows physical connections between the dynamical system and the data-based model such as the evolution of the system over time.

Enhancing the quality of evidence, comparability, and reproducibility in brain arteriovenous malformations treated with open surgery research: a systematic review and proposal of a reporting guideline for surgical and clinical outcomes.

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

Functional lateralization in the medial prefrontal cortex control of contextual conditioned emotional responses in rats.

A functional lateralization has been reported in control of emotional responses by the medial prefrontal cortex (mPFC). However, a hemisphere asymmetry in involvement of the mPFC in expression of fear conditioning responses has never been reported. Therefore, we investigated whether control by mPFC of freezing and cardiovascular responses during re-exposure to an aversively conditioned context is lateralized. For this, rats had guide cannulas directed to the mPFC implanted bilaterally or unilaterally in the right or left hemispheres. Vehicle or the non-selective synaptic inhibitor CoCl2 was microinjected into the mPFC 10 min before re-exposure to a chamber where the animals had previously received footshocks. A catheter was implanted into the femoral artery before the fear retrieval test for cardiovascular recordings. We observed that bilateral microinjection of CoCl2 into the mPFC reduced both the freezing behavior (enhancing locomotion and rearing) and arterial pressure and heart rate increases during re-exposure to the aversively conditioned context. Unilateral microinjection of CoCl2 into the right hemisphere of the mPFC also decreased the freezing behavior (enhancing locomotion and rearing), but without affecting the cardiovascular changes. Conversely, unilateral synaptic inhibition in the left mPFC did not affect either behavioral or cardiovascular responses during fear retrieval test. Taken together, these results suggest that the right hemisphere of the mPFC is necessary and sufficient for expression of freezing behavior to contextual fear conditioning. However, the control of cardiovascular responses and freezing behavior during fear retrieval test is somehow dissociated in the mPFC, being the former bilaterally processed.

The Risk of Reinfection or Primary Hepatitis E Virus Infection at a Liver Transplant Center in Brazil: An Observational Cohort Study.

The hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Seroprevalence in the liver transplantation setting varies according to the seroprevalence of the general population in different countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 10.2% of the recipients and in 9.7% of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation.

Spatial analysis of Dengue through the reproduction numbers relating to socioeconomic features: Case studies on two Brazilian urban centers.

The study of the propagation of infectious diseases in urban centers finds a close connection with their population's social characteristics and behavior. This work performs a spatial analysis of dengue cases in urban centers based on the basic reproduction numbers, R0, and incidence by planning areas (PAs), as well as their correlations with the Human Development Index (HDI) and the number of trips. We analyzed dengue epidemics in 2002 at two Brazilian urban centers, Belo Horizonte (BH) and Rio de Janeiro (RJ), using PAs as spatial units. Our results reveal heterogeneous spatial scenarios for both cities, with very weak correlations between R0 and both the number of trips and the HDI; in BH, the values of R0 show a less spatial heterogeneous pattern than in RJ. For BH, there are moderate correlations between incidence and both the number of trips and the HDI; meanwhile, they weakly correlate for RJ. Finally, the absence of strong correlations between the considered measures indicates that the transmission process should be treated considering the city as a whole.

Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia.

Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.

Early Initiation of PCSK9 Inhibitor Therapy Versus Placebo in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, p = 0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined.