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The capacity of environmental pollutants to generate oxidative stress is known to affect the development and progression of chronic diseases. This scientific review identifies previously published experimental studies using preclinical models of exposure to environmental stress agents, such as black carbon and/or RF-EMF, which produce cellular oxidative damage and can lead to different types of cell death. We summarize in vivo and in vitro studies, which are grouped according to the mechanisms and pathways of redox activation triggered by exposure to BC and/or EMF and leading to apoptosis, necrosis, necroptosis, pyroptosis, autophagy, ferroptosis and cuproptosis. The possible mechanisms are considered in relation to the organ, cell type and cellular-subcellular interaction with the oxidative toxicity caused by BC and/or EMF at the molecular level. The actions of these environmental pollutants, which affect everyday life, are considered separately and together in experimental preclinical models. However, for overall interpretation of the data, toxicological studies must first be conducted in humans, to enable possible risks to human health to be established in relation to the progression of chronic diseases. Further actions should take pollution levels into account, focusing on the most vulnerable populations and future generations.

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The ability to hold objects relies on neural processes underlying grip force control during grasping. Brain activity lateralized to contralateral hemisphere averaged over trials is associated with grip force applied on an object. However, the involvement of neural variability within-trial during grip force control remains unclear. We examined dependence of neural variability over frontal, central, and parietal regions of interest (ROI) on grip force magnitude using noninvasive electroencephalography (EEG). We utilized our existing EEG dataset comprised of healthy young adults performing an isometric force control task, cued to exert 5, 10, or 15% of their maximum voluntary contraction (MVC) across trials and received visual feedback of their grip force. We quantified variability in EEG signal via sample entropy (sequence-dependent) and standard deviation (sequence-independent measure) over ROI. We found lateralized modulation in EEG sample entropy with force magnitude over central electrodes but not over frontal or parietal electrodes. However, modulation was not observed for standard deviation in the EEG activity. These findings highlight lateralized and spatially constrained modulation in sequence-dependent, but not sequence-independent component of EEG variability. We contextualize these findings in applications requiring finer precision (e.g., prosthesis), and propose directions for future studies investigating role of neural entropy in behavior.

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Balance control is an important indicator of mobility and independence in activities of daily living. How the functional coupling between the cortex and the muscle for balance control is affected following stroke remains to be known. We investigated the changes in coupling between the cortex and leg muscles during a challenging balance task over multiple frequency bands in chronic stroke survivors. Fourteen participants with stroke and ten healthy controls performed a challenging balance task. They stood on a computerized support surface that was either fixed (low difficulty condition) or sway-referenced with varying gain (medium and high difficulty conditions). We computed corticomuscular coherence between electrodes placed over the sensorimotor area (electroencephalography) and leg muscles (electromyography) and assessed balance performance using clinical and laboratory-based tests. We found significantly lower delta frequency band coherence in stroke participants when compared with healthy controls under medium difficulty condition, but not during low and high difficulty conditions. These differences were found for most of the distal but not for proximal leg muscle groups. No differences were found at other frequency bands. Participants with stroke showed poor balance clinical scores when compared with healthy controls, but no differences were found for laboratory-based tests. The observation of effects at distal but not at proximal muscle groups suggests differences in the (re)organization of the descending connections across two muscle groups for balance control. We argue that the observed group difference in delta band coherence indicates balance context-dependent alteration in mechanisms for the detection of somatosensory modulation resulting from sway-referencing of the support surface for balance maintenance following stroke.

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ABSTRACT: A phase 2, international, open-label, nonrandomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL received tipifarnib 300 mg orally twice daily for 21 days in a 28-day cycle. The primary end point was objective response rate (ORR); secondary end points included ORR, progression-free survival (PFS), duration of response (DOR), and adverse events (AEs) in specific subtypes. Sixty-five patients with PTCL were enrolled: n = 38 angioimmunoblastic T-cell lymphoma (AITL), n = 25 PTCL not otherwise specified, and n = 2 other T-cell lymphomas. The ORR was 39.7% (95% confidence interval [CI], 28.1-52.5) in all patients and 56.3% (95% CI, 39.3-71.8) for AITL. Median PFS was 3.5 months overall (954% CI, 2.1-4.4), and 3.6 months (95% CI, 1.9-8.3) for AITL. Median DOR was 3.7 months (95% CI, 2.0-15.3), and greatest in patients with AITL (7.8 months; 95% CI, 2.0-16.3). The median overall survival was 32.8 months (95% CI, 14.4 to not applicable). Tipifarnib-related hematologic AEs were manageable and included neutropenia (43.1%), thrombocytopenia (36.9%), and anemia (30.8%); other tipifarnib-related AEs included nausea (29.2%) and diarrhea (27.7%). One treatment-related death occurred. Mutations in RhoA, DNMT3A, and IDH2 were seen in 60%, 33%, and 27%, respectively, in the AITL tipifarnib responder group vs 36%, 9%, and 9% in the nonresponder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pretreated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. This trial was registered at www.ClinicalTrials.gov as #NCT02464228.

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No accurate and rapid diagnostic test exists for tuberculous meningitis (TBM), leading to delayed diagnosis. We leveraged data from multiple studies to improve the predictive performance of diagnostic models across different populations, settings, and subgroups to develop a new predictive tool for TBM diagnosis. We conducted a systematic review to analyze eligible datasets with individual-level participant data (IPD). We imputed missing data and explored three approaches: stepwise logistic regression, classification and regression tree (CART), and random forest regression. We evaluated performance using calibration plots and C-statistics via internal-external cross-validation. We included 3,761 individual participants from 14 studies and nine countries. A total of 1,240 (33%) participants had "definite" (30%) or "probable" (3%) TBM by case definition. Important predictive variables included cerebrospinal fluid (CSF) glucose, blood glucose, CSF white cell count, CSF differential, cryptococcal antigen, HIV status, and fever presence. Internal validation showed that performance varied considerably between IPD datasets with C-statistic values between 0.60 and 0.89. In external validation, CART performed the worst (C = 0.82), and logistic regression and random forest had the same accuracy (C = 0.91). We developed a mobile app for TBM clinical prediction that accounted for heterogeneity and improved diagnostic performance (https://tbmcalc.github.io/tbmcalc). Further external validation is needed.

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BACKGROUND: The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. METHODS: All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. RESULTS: We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). CONCLUSION: In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.

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BACKGROUND: Epidemiological studies on predisposing conditions and outcomes of progressive multifocal leukoencephalopathy (PML) cases have been carried out exclusively in high-income countries. We aim to report and compare the main characteristics and outcomes of patients with PML and several underlying diseases in a referral center in a middle-income country. METHODS: We performed a retrospective cohort study of PML cases admitted to a tertiary care hospital in São Paulo, Brazil during 2000-2022. Demographic and PML-specific variables were recorded. One-year case-fatality rate and factors associated with death were identified using a multivariate Cox proportional hazards regression model. RESULTS: Ninety-nine patients with PML were included. HIV infection (84.8%) and malignancy (14.1%) were the most prevalent underlying conditions. Other predisposing diseases were autoimmune/inflammatory diseases (5.1%) and solid organ transplantation (1.0%). One (1.0%) patient had liver cirrhosis and another (1.0%) patient was previously healthy. Focal motor deficits (64.2%) and gait instability (55.1%) were the most common signs. The one-year case-fatality rate was 52.5% (95% CI 42.2-62.7). The one-year case-fatality rate (95% CI) in patients with or without malignancy (85.7%, 95% CI 57.2-98.2% and 47.1%, 95% CI 36.1-58.2%, respectively) were statistically different (P = 0.009). Crude and adjusted Cox regression models identified malignancy as independently associated with death (adjusted HR = 3.92, 95% CI 1.76-8.73, P = 0.001). CONCLUSIONS: HIV/AIDS was the predisposing condition in 84.8% of PML cases. The one-year case-fatality rate was 52.5% and having a malignancy was independently associated with death. This study reports emerging data on the epidemiology and outcome of PML in a middle-income country.

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Background: Arterial hypertension is highly prevalent in Mexico; nevertheless, there are limited insights regarding its management during the COVID-19 pandemic. Here, we estimate the prevalence of clinical and treatment profiles of arterial hypertension and explore associated factors for undiagnosed and uncontrolled hypertension using a cross-sectional survey endorsed by the Collaborative Group on Arterial Hypertension from the Mexican Institute of Social Security. Methods: Our survey was conducted from May to November 2021 using the May-Measurement Month 2021 protocols of the International Society of Hypertension. Arterial hypertension (defined as: blood pressure [BP] ≥140/90 mmHg, previous diagnosis, or taking antihypertensives) and its clinical and treatment profiles were classified according to the World Hypertension League Expert Committee. Mixed-effects logistic regression models were used to explore associated factors for undiagnosed and uncontrolled hypertension. Results: Among 77,145 screened participants (women: 62.4%; median age: 46 [IQR: 32-59] years), the prevalence of arterial hypertension was 35.7% (95% CI: 35.3-36.0, n = 27,540). Among participants with arterial hypertension, 30.9% (95% CI: 30.4-31.5, n = 8,533) were undiagnosed, 6.6% (95% CI: 6.3%-6.9%, n = 1,806) were diagnosed but untreated, 43.4% (95% CI: 42.9-44.0, n = 11,965) had uncontrolled hypertension, and only 19% (95% CI: 18.6%-19.5%, n = 5,236) achieved hypertension control (BP < 130/80 mmHg). Explored associated factors for undiagnosed and uncontrolled hypertension include being men, living in the central and southern regions, lower educational attainments, higher use of pharmacological agents, and previous COVID-19 infection. Conclusion: Our findings suggest that adverse arterial hypertension profiles, mainly undiagnosed and uncontrolled hypertension, were highly prevalent during the context of the COVID-19 pandemic in Mexico.

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BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

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Resumen El diagnóstico electrocardiográfico de infarto agudo de miocardio (IAM) en el paciente con marcapasos siempre ha sido un problema en la práctica clínica, provocando retrasos en el manejo y peores desenlaces clínicos. Aunque el bloqueo completo de rama izquierda (BCRI) y la estimulación del ventrículo derecho pueden producir anomalías en el electrocardiograma (ECG), cambios morfológicos específicos a menudo permiten el diagnóstico de IAM o un infarto antiguo. Reporte de caso: Paciente de 76 años con antecedente de implante de marcapasos definitivo por bloqueo auriculoventricular de 3° grado, que ingresó por dolor precordial. A su ingreso hemodinámicamente estable, pero con ECG que muestra ritmo de marcapasos con BCRI cumpliendo Sgarbossa 2 puntos (elevación discordante del segmento ST > 5 mm en derivaciones V1 a V3) y relación ST/S < -0.25 en derivaciones V3-V4. Laboratorios con elevación de troponinas, integrándose diagnóstico de IAM y pasando a angiografía coronaria urgente. Se documentó lesión en arteria coronaria descendente anterior y se implantó stent liberador de fármaco angiográficamente exitoso. Se egresó estable, asintomático y con manejo farmacológico para prevención secundaria. Conclusión: La identificación por ECG de un IAM en pacientes portadores de marcapasos es fundamental para iniciar terapia de reperfusión. Las recomendaciones de las guías cambian constantemente, pero un algoritmo que utiliza la inestabilidad hemodinámica y los criterios de Sgarbossa modificados (CSM) para decidir el manejo de estos pacientes pudiera ser una herramienta con una alta sensibilidad y permitirá a los médicos tener la mejor toma de decisiones sin esperar resultados de laboratorio. Los CSM, que son más sensibles que los criterios originales, continúan siendo útiles en el diagnóstico de IAM. Los médicos deben elegir cuidadosamente el límite de CSM apropiado (relación ST/T -0.20 y -0.25) de acuerdo con cada caso.

Abstract The electrocardiographic diagnosis of acute myocardial infarction (AMI) in patients with pacemakers has always been a problem in clinical practice, causing delays in management and worse clinical outcomes. Although complete left bundle branch block (LBBB) and right ventricular pacing can produce electrocardiogram (ECG) abnormalities, specific morphological changes often allow the diagnosis of AMI or an old infarction. Case report: A 76-year-old patient with history of permanent pacemaker implantation due to a 3rd-degree atrioventricular block was admitted for chest pain. Upon admission, he was hemodynamically stable but with ECG showing pacemaker rhythm with LBBB fulfilling 2 points of Sgarbossa criteria (discordant elevation of the ST segment > 5 mm in leads V1 to V3) and ST/S ratio < -0.25 in leads V3-V4. Laboratories showed elevated troponins, integrating diagnosis of AMI, and moving on to urgent coronary angiography. A lesion on the anterior descending coronary artery was documented, and a drug-eluting stent was successfully implanted. The patient was discharged stable, asymptomatic, and with pharmacological management for secondary prevention. Conclusion: ECG identification of an AMI in patients with pacemakers is essential to initiate reperfusion therapy. Guideline recommendations are constantly changing, but an algorithm that uses hemodynamic instability and the modified Sgarbossa criteria (MSC) to decide these patients' management could be a high-sensitivity tool and allow physicians to make the best decisions without waiting for laboratory results. MSC, which are more sensitive than the original criteria, continue to be helpful in the diagnosis of AMI. Clinicians should carefully choose the appropriate MSC cut-off (ST/T Ratio -0.20 and -0.25) on a case-by-case basis.

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OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.

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INTRODUCTION: We systematically assessed benefits and harms of the use of ivermectin in non-hospitalized patients with early COVID-19. METHODS: Five databases were searched until October 17, 2023, for randomized controlled trials (RCTs) in adult patients with COVID-19 treated with ivermectin against standard of care (SoC), placebo, or active drug. Primary outcomes were hospitalization, all-cause mortality, and adverse events (AEs). Secondary outcomes included mechanical ventilation (MV), clinical improvement, clinical worsening, viral clearance, and severe adverse events (SAEs). Random effects meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Pre-specified subgroup analyses (ivermectin dose, control type, risk of bias, follow-up, and country income) and trial sequential analysis (TSA) were performed. RESULTS: Twelve RCTs (n = 7,035) were included. The controls were placebo in nine RCTs, SoC in two RCTs, and placebo or active drug in one RCT. Ivermectin did not reduce hospitalization (relative risk [RR], 0.81, 95% confidence interval [95% CI] 0.64-1.03; 8 RCTs, low QoE), all-cause mortality (RR 0.98, 95% CI 0.73-1.33; 9 RCTs, low QoE), or AEs (RR 0.89, 95% CI 0.75-1.07; 9 RCTs, very low QoE) vs. controls. Ivermectin did not reduce MV, clinical worsening, or SAEs and did not increase clinical improvement and viral clearance vs. controls (very low QoE for secondary outcomes). Subgroup analyses were mostly consistent with main analyses, and TSA-adjusted risk for hospitalization was similar to main analysis. CONCLUSIONS: In non-hospitalized COVID-19 patients, ivermectin did not have effect on clinical, non-clinical or safety outcomes versus controls. Ivermectin should not be recommended as treatment in non-hospitalized COVID-19 patients.

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OBJECTIVE: Motor imagery-based brain-computer interface (MI-BCI) is a promising novel mode of stroke rehabilitation. The current study aims to investigate the feasibility of MI-BCI in upper limb rehabilitation of chronic stroke survivors and also to study the early event-related desynchronization after MI-BCI intervention. METHODS: Changes in the characteristics of sensorimotor rhythm modulations in response to a short brain-computer interface (BCI) intervention for upper limb rehabilitation of stroke-disabled hand and normal hand were examined. The participants were trained to modulate their brain rhythms through motor imagery or execution during calibration, and they played a virtual marble game during the feedback session, where the movement of the marble was controlled by their sensorimotor rhythm. RESULTS: Ipsilesional and contralesional activities were observed in the brain during the upper limb rehabilitation using BCI intervention. All the participants were able to successfully control the position of the virtual marble using their sensorimotor rhythm. CONCLUSIONS: The preliminary results support the feasibility of BCI in upper limb rehabilitation and unveil the capability of MI-BCI as a promising medical intervention. This study provides a strong platform for clinicians to build upon new strategies for stroke rehabilitation by integrating MI-BCI with various therapeutic options to induce neural plasticity and recovery.

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BACKGROUND: This research focused on the development of a motor imagery (MI) based brain-machine interface (BMI) using deep learning algorithms to control a lower-limb robotic exoskeleton. The study aimed to overcome the limitations of traditional BMI approaches by leveraging the advantages of deep learning, such as automated feature extraction and transfer learning. The experimental protocol to evaluate the BMI was designed as asynchronous, allowing subjects to perform mental tasks at their own will. METHODS: A total of five healthy able-bodied subjects were enrolled in this study to participate in a series of experimental sessions. The brain signals from two of these sessions were used to develop a generic deep learning model through transfer learning. Subsequently, this model was fine-tuned during the remaining sessions and subjected to evaluation. Three distinct deep learning approaches were compared: one that did not undergo fine-tuning, another that fine-tuned all layers of the model, and a third one that fine-tuned only the last three layers. The evaluation phase involved the exclusive closed-loop control of the exoskeleton device by the participants' neural activity using the second deep learning approach for the decoding. RESULTS: The three deep learning approaches were assessed in comparison to an approach based on spatial features that was trained for each subject and experimental session, demonstrating their superior performance. Interestingly, the deep learning approach without fine-tuning achieved comparable performance to the features-based approach, indicating that a generic model trained on data from different individuals and previous sessions can yield similar efficacy. Among the three deep learning approaches compared, fine-tuning all layer weights demonstrated the highest performance. CONCLUSION: This research represents an initial stride toward future calibration-free methods. Despite the efforts to diminish calibration time by leveraging data from other subjects, complete elimination proved unattainable. The study's discoveries hold notable significance for advancing calibration-free approaches, offering the promise of minimizing the need for training trials. Furthermore, the experimental evaluation protocol employed in this study aimed to replicate real-life scenarios, granting participants a higher degree of autonomy in decision-making regarding actions such as walking or stopping gait.

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Chagas' disease reactivation leading to monophasic acute or subacute meningoencephalitis or space-occupying lesions is a well-described AIDS-defining condition in Latin America. We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas' disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic disease.

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INTRODUCTION: The recurrent nature of hidradenitis suppurativa (HS), even under maintained systemic treatment, makes it necessary to have effective local treatments; however, the response to these therapies is variable (44-81%). The application of galvanic current (GC) has demonstrated its utility in humans in treating lesions structurally similar to those of HS. With this background, the main objective of this study was to evaluate the efficacy and safety of ultrasound-guided percutaneous GC in inflamed and/or draining tunnels of HS. METHODS: This was an open study (one-way repeated measures design over time). Patients were evaluated at 4 and 12 weeks after receiving GC. A combined clinical response at week 12 (absence of suppuration/inflammation on examination and clinical interview) was considered the principal variable of efficacy. Adverse effects potentially associated with GC were reported by telephone and at each visit. RESULTS: Twenty-six patients were included, with a male/female ratio of 5:8. The mean age was 35.84 (13.14) years. At 12 weeks after the administration of GC, a complete response was achieved in 77% (20/26) of the treated lesions. No serious adverse effects were observed, and the mean procedural pain assessed by the numeric rating scale was 0.03 (0.2). CONCLUSION: GC has proven to be effective and well tolerated in inflamed and draining tunnels of patients with HS.

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Four cases of people living with HIV/AIDS (PLWHA) with calcified cerebral toxoplasmosis associated with perilesional edema causing a single episode of neurological manifestations have recently been reported. Here, we describe the first detailed description of perilesional edema associated with calcified cerebral toxoplasmosis causing three episodes of neurological manifestations in a PLWHA, including seizures in two of them. These recurrences occurred over approximately a decade. Throughout this period, the patient showed immunological and virological control of the HIV infection, while using antiretroviral therapy regularly. This case broadens the spectrum of an emerging presentation of calcified cerebral toxoplasmosis, mimicking a well-described finding of neurocysticercosis in immunocompetent hosts.

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PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

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Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

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