Acute diarrhea in the hospitalized immunocompromised patient: what is new on diagnostic and treatment?

PURPOSE OF THIS REVIEW: This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. RECENT FINDINGS: Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. SUMMARY: Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts.

Introduction: While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Methods: Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders. Results: Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort. Discussion: Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.

Case report: CMV retinitis following local and systemic immunosuppression.

We report the case of a 71-year-old man who presented 2 years following renal transplantation with diffuse, unilateral cytomegalovirus retinitis five weeks after receiving an intravitreal dexamethasone implant device for the management of central retinal vein occlusion. Examination of the left eye showed diffuse retinal hemorrhages, attenuated and tortuous retinal vessels, and superior retinal whitening. The patient was successfully treated with serial intravitreal foscarnet injections and oral valganciclovir with disease regression observed by 12 weeks after presentation. The patient's visual acuity and examination remained stable at 9-months follow-up.

Predicting immune checkpoint therapy response in three independent metastatic melanoma cohorts.

While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders. Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort. Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.

Rapid discrimination of geographical origin of garlic (Allium sativum L.): A metabolomic approach applied to paper spray mass spectrometry data.

INTRODUCTION: Distinguishing and categorizing the origin of garlic are highly significant, considering its widespread use as a flavoring agent. With billions of dollars annually in global trade, garlic is frequently susceptible to fraudulent practices. METHODOLOGY: Paper spray ionization mass spectrometry (PS-MS) was employed to quickly analyze garlic samples from distinct geographic origins: China and Brazil. The so-generated PS-MS data were treated with metabolomic multivariate approaches, and the garlic samples from these different geographic regions were easily discriminated. RESULTS: Brazilian garlic was characterized to contain higher levels of amino acids, such as arginine, proline, and valine, and organosulfur compounds, such as allicin, alliin, and l-γ-glutamil-S-allyl-l-cysteine, compared to Chinese garlic. The PS-MS data were treated employing multivariate approaches, typically used in the metabolomics field, and this protocol was promptly able to discern among both types of samples. CONCLUSION: Hence, this combined strategy holds promise not only as an effective tool for the authentication of the geographical origin of garlic but also as a powerful means for biomarker discovery.

Identifying Ferroptosis Inducers, HDAC, and RTK Inhibitor Sensitivity in Melanoma Subtypes through Unbiased Drug Target Prediction.

The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem. Here we mine large scale MM proteogenomic data integrating it with MM cell line dependency screen, and drug sensitivity data to identify druggable targets and forecast treatment efficacy and resistance. Leveraging protein profiles from established MM subtypes and molecular structures of 82 cancer treatment drugs, we identified nine candidate hub proteins, mTOR, FYN, PIK3CB, EGFR, MAPK3, MAP4K1, MAP2K1, SRC and AKT1, across five distinct MM subtypes. These proteins serve as potential drug targets applicable to one or multiple MM subtypes. By analyzing transcriptomic data from 48 publicly accessible melanoma cell lines sourced from Achilles and CRISPR dependency screens, we forecasted 162 potentially targetable genes. We also identified genetic resistance in 260 genes across at least one melanoma subtype. In addition, we employed publicly available compound sensitivity data (Cancer Therapeutics Response Portal, CTRPv2) on the cell lines to assess the correlation of compound effectiveness within each subtype. We have identified 20 compounds exhibiting potential drug impact in at least one melanoma subtype. Remarkably, employing this unbiased approach, we have uncovered compounds targeting ferroptosis, that demonstrate a striking 30x fold difference in sensitivity among different subtypes. This implies that the proteogenomic classification of melanoma has the potential to predict sensitivity to ferroptosis compounds. Our results suggest innovative and novel therapeutic strategies by stratifying melanoma samples through proteomic profiling, offering a spectrum of novel therapeutic interventions and prospects for combination therapy. Highlights: (1) Proteogenomic subtype classification can define the landscape of genetic dependencies in melanoma (2) Nine proteins from molecular subtypes were identified as potential drug targets for specified MM patients (3) 20 compounds identified that show potential effectiveness in at least one melanoma subtype (4) Proteogenomics can predict specific ferroptosis inducers, HDAC, and RTK Inhibitor sensitivity in melanoma subtypes.

Determination of the volatile chemical profile of Momordica charantia (bitter melon) leaf and fruit by GC-MS.

The plant Momordica charantia (Cucurbitaceae), popularly known as bitter melon, snake fruit, Saint Vincent's herb, or little melon, is an African species that has developed in tropical and subtropical biomes in various parts of Brazil. The fruit is used in various traditional medicinal applications. The study aimed to identify the compounds of the essential oil of the leaves obtained by hydrodistillation and in the fruit through Solid-Phase Microextraction by headspace mode (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS). The analysis of mature fruits led to the identification of 18 compounds, compared to the hydrodistillation, in which 21 compounds were identified. Benzaldehyde, linalool, and ß-cyclocitral were identified in both methods. Linalool was the major compound in both processes. These findings highlight the importance of knowing the chemical composition of organic volatile compounds (VOCs), given the potential for medicinal applications and popular use of plants.

Reconsidering the role of nasolabial angle in premolar extraction decision-making: A case-series study.

OBJECTIVES: To evaluate the impact of changes in upper incisor inclination and position on the alteration of the nasolabial angle (NLA) in a series of cases involving the extraction of four first premolars. MATERIALS AND METHODS: The study included 41 patients who underwent orthodontic treatment with premolar extractions. The patients were divided into two groups based on their pretreatment NLA values: Group 1 (NLA ≤ 100°) and Group 2 (NLA > 100°). Measurements of NLA, U1.NA and U1-NA were obtained before and after treatment and U1-Ls pretreatment measure was registered. Statistical analyses were performed to compare the differences in NLA, U1.NA and U1-NA between the two groups and to evaluate the influence of these variables added to U1-Ls (T1) on NLA changes. RESULTS: The results showed that Group 1 exhibited significant changes in NLA, while Group 2 did not. However, both groups showed significant changes in U1.NA and U1-NA. In Group 1, 80% of the individuals presented an increase in NLA and 20% no changes. In Group 2, 10% presented a decrease, 57% no changes and 33% an increase in NLA values. Multiple linear regression analysis indicated that the group factor had a statistically significant influence on NLA variation. Additionally, in Group 2, a negative correlation was observed between changes in U1.NA and NLA. CONCLUSIONS: The findings suggest that individuals with higher pretreatment NLA values tend to maintain their NLA values even after the correction of upper incisor inclination.

Impact of the COVID-19 pandemic on the symptomatology and routine of medicated patients with obsessive-compulsive disorder.

OBJECTIVES: To study the impact of coronavirus disease 2019 on the routine of patients with obsessive-compulsive disorder (OCD) and changes in symptoms and suicidal-related behavior, mainly in those with cleaning symptoms. METHODS: In this cross-sectional study, 58 patients completed an online self-report questionnaire that included the Obsessive-Compulsive Inventory-Revised, Coronavirus Stress and Traumatic Events Scale, Coronavirus Health Impact Survey, Beck Anxiety and Beck Depression inventories, and Suicide-Related Behaviors Questionnaire. Comparisons were made with another pre-pandemic sample (n=524) regarding the last three measures. RESULTS: During the pandemic, the patients spent more days inside their homes (χ² = 33.39, p = 0.007), changed their alcohol consumption patterns (χ² = 87.6, p < 0.001), and increased social media usage (χ² = 68.83, p < 0.001). Participants with cleaning symptoms did not significantly differ from the others in relation to stress, anxiety/depressive symptoms, or suicidal-related behaviors. Finally, our sample did not differ from an equivalent OCD sample assessed before the pandemic in terms of anxiety and depressive symptom severity or suicidal-related behaviors. CONCLUSION: Overall, patients with OCD showed no lifestyle changes associated with higher stress levels during the pandemic. Patients with and without cleaning symptoms and patients before and during the pandemic presented similar results.

Plasmodium chabaudi Merozoites Obtained through a Simpler Method Do Not Survive in Classically Activated Macrophages.

Malaria is caused by apicomplexan parasites of the Plasmodium genus. Plasmodium chabaudi is an excellent animal model for the study of human malaria caused by P. falciparum. Merozoites invade erythrocytes but are also found in other host cells including macrophages from the spleen and liver. Methodologies for obtaining merozoites usually involve treatment with protease inhibitors. However, merozoites obtained in this way may have their enzymatic profile altered and, therefore, are not ideal for cell-interaction assays. We report the obtainment of P. chabaudi merozoites naturally egressed from a synchronous erythrocyte population infected with schizonts forms. Merozoites had their infectivity and ultrastructure analyzed. Interaction assays were performed with mice erythrocytes and classically activated mice peritoneal macrophages, a very well-established classic model. Obtained merozoites were able to kill mice and efficiently infect erythrocytes. Interestingly, a lower merozoite:erythrocyte ratio resulted in a higher percentage of infected erythrocytes. We describe a simpler method for obtaining viable and infective merozoites. Classically activated macrophages killed merozoites, suggesting that these host cells may not serve as reservoirs for these parasites. These findings have implications for our understanding of P. chabaudi merozoite biology and may improve the comprehension of their host-parasite relationship.

Impact of the COVID-19 pandemic on the symptomatology and routine of medicated patients with obsessive-compulsive disorder

Objectives: To study the impact of coronavirus disease 2019 on the routine of patients with obsessive-compulsive disorder (OCD) and changes in symptoms and suicidal-related behavior, mainly in those with cleaning symptoms. Methods: In this cross-sectional study, 58 patients completed an online self-report questionnaire that included the Obsessive-Compulsive Inventory-Revised, Coronavirus Stress and Traumatic Events Scale, Coronavirus Health Impact Survey, Beck Anxiety and Beck Depression inventories, and Suicide-Related Behaviors Questionnaire. Comparisons were made with another pre-pandemic sample (n=524) regarding the last three measures. Results: During the pandemic, the patients spent more days inside their homes (χ2 = 33.39, p = 0.007), changed their alcohol consumption patterns (χ2 = 87.6, p < 0.001), and increased social media usage (χ2 = 68.83, p < 0.001). Participants with cleaning symptoms did not significantly differ from the others in relation to stress, anxiety/depressive symptoms, or suicidal-related behaviors. Finally, our sample did not differ from an equivalent OCD sample assessed before the pandemic in terms of anxiety and depressive symptom severity or suicidal-related behaviors. Conclusion: Overall, patients with OCD showed no lifestyle changes associated with higher stress levels during the pandemic. Patients with and without cleaning symptoms and patients before and during the pandemic presented similar results.

How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

Diversity of vegetable landraces in the Pampa biome of Brazil and Uruguay: utilization and conservation strategies.

The historical meeting between originally American people, European colonizers, and slaved peoples from Africa in the biome Pampa in South Brazil and Uruguay involved a cultural syncretism and a great genetic diversity of landraces of cultivated species. Genetic richness evolved by selection and cultural processes in response to different environments, cultural backgrounds, and needs. This review summarized the knowledge on vegetable and maize landraces in South Brazilian and Uruguayan Pampa biome, to design a strategy towards the rediscovery, conservation, and sustainable use. Landraces diversity maintained in situ and ex situ is described, specific case studies are presented, and the main problems and tools towards landraces re-valorization are discussed. We show that traditional family farming systems maintain diverse vegetable species, mainly squashes (Cucurbita spp.), sweet potato (Ipomoea batatas), beans (Phaseolus spp.), onion (Allium cepa), peppers (Capsicum spp.), tomato (Solanum lycopersicum), next to leafy vegetables and maize, among others. We propose the priority of systematic surveys as a basis for monitoring genetic erosion, increasing complementariness between in situ and ex situ conservation, and implementing sustainable conservation and utilization. The case studies highlight genetic diversity within each cultivated species, with different crop physiological responses; disease resistances, different quality traits and associated uses, from animal feeding in maize to a range of culinary uses linked to traditional culture in maize and vegetable species, and ornamental uses of specific Capsicum and Cucurbita. Some landraces were the basis for breeding, where improved cultivars allowed the competitiveness of landrace germplasm in the markets. Renewed industrialized products allowed the competitive and sustainable use of Capsicum landraces in Brazilian farmers communities. Strategies towards in situ conservation improvements and valorization are discussed; emphasizing the role played by agroecology, community seed banks and custodian farmers, participatory plant breeding, promotion of landraces specialties among consumers, and the need of research and capacity building, among others. Farmers' participation in the decisions is a key factor, along with the academia and the public sector. Landraces and associated knowledge are treasures to be used to benefit from farmers to consumers, directing the course of agriculture towards sustainable directions.

The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Polymorphisms and avascular necrosis in patients with sickle cell disease - A systematic review.

OBJECTIVE: To systematically establish whether there is an association between polymorphisms and avascular necrosis in patients with sickle cell disease. DATA SOURCE: The review, conducted according to PRISMA guidelines and registered with PROSPERO, was based on research of studies in PubMed, SciELO, LILACS, BVS databases and in the gray literature (Google Scholar and Open Gray) published until June 2020. The STROBE initiative was used to analyze the articles' quality. DATA SYNTHESIS: Ten articles were selected from the databases and two were included through manual search, totaling 12 studies. All samples gathered 2,362 patients. According to STROBE, seven studies fully and/or partially covered more than 70% of the essential items and two studies reached less than 60%, with an overall variation of 86.4-54.5%. The results indicate that polymorphisms in the genes of the bone morphogenetic protein 6 (BMP6), Klotho (KL) and Annexin A2 (ANXA2) may be associated with osteonecrosis in the context of sickle cell disease. Six articles addressed the polymorphism in the MTHFR enzyme gene, but only one found a positive association. Polymorphisms associated with the DARC receptor, the ITGA4 gene, CD36 and thrombophilia protein genes were not associated in any of the studies. CONCLUSIONS: The results indicate that the polymorphisms in BMP6, Klotho and ANXA2 genes may be associated with avascular necrosis in patients with sickle cell disease. However, in order to confirm these genetic changes as risk factors, further studies with greater statistical power and methodological rigor are needed.

Serum levels of olanzapine are associated with acute cognitive effects in bipolar disorder.

Bipolar (BPD) patients have deficits in cognition, but there are still controversies about the effects of some medications on their cognitive performance. Here, we investigated the relationship between cognition in terms of executive functions, memory, and attention in both first-episode medication-naive BPD patients and BPD patients taking olanzapine. Forty-one healthy controls, 40 unmedicated drug-naive BPD patients, and 34 BPD patients who took only olanzapine were recruited for the study. Cognitive performance was assessed using the Flanker test, Stroop test, and Corsi-block test. Bayesian multivariate regression analysis was run considering maximum robustness to avoid bias and to predict the outcomes. Our results revealed that unmedicated medication-naive BPD patients performed worse than healthy controls and the olanzapine group in some tasks. Additionally, BPD patients who took olanzapine had better cognitive performance than healthy controls and unmedicated BPD patients. The acute cognitive effects were predicted by olanzapine dosage and serum levels (i.e., large effects). The potential pro-cognitive effects of olanzapine in BPD patients should be carefully interpreted by considering various other clinical variables. We expect that our findings will contribute to further research in this area, with the goal of helping other researchers, patients, and the population.