Tuberculosis case notifications and outcomes in Peruvian prisons prior to and during the COVID-19 pandemic: a national-level interrupted time series analysis.

Background: The COVID-19 pandemic has significantly disrupted tuberculosis (TB) programs, making it urgent to focus TB elimination efforts on key populations. People experiencing incarceration are at high risk for TB, however, how COVID-19-related disruptions have impacted incarcerated populations with TB is unknown. Methods: Using Peruvian National TB Program data from Jan 2018 to Dec 2021, an interrupted time series of drug-susceptible (DS) TB case notifications pre- and during COVID-19 was conducted (cut-off date: COVID-19 emergency declaration in Peru, 16 March 2020). The effect of TB care occurring pre-vs. during COVID-19 on TB treatment success in the incarcerated and non-incarcerated populations was explored using logistic regression. Findings: DS-TB cases notified in prisons from Jan 2018 to Dec 2021 (n = 10,134) represented 10% of all cases notified in the country (n = 101,507). In the first week of COVID-19, DS-TB case notifications dropped by 61.2% (95% CI: 59.9-62.7%) in the non-incarcerated population and 17.7% (95% CI: 17.5-17.9%) among the incarcerated population. TB treatment success was significantly lower in people receiving TB care entirely during the COVID-19 pandemic vs. before COVID-19 in the non-incarcerated population (OR: 0.81, 95% CI: 0.78-0.85), but not statistically significantly lower in the incarcerated population (OR: 0.88, 95% CI: 0.76-1.01). Incarceration status was not found to modify the effect of COVID-19 period on TB treatment outcomes (OR: 1.07, 95% CI: 0.92-1.25), although treatment success was higher in the incarcerated population (OR [incarcerated vs. not incarcerated, pre-COVID]: 1.52, 95% CI: 1.39-1.67). Interpretation: Both incarcerated and non-incarcerated populations experienced a large drop in DS-TB case notifications (although higher in the non-incarcerated population). Lower TB treatment success among those receiving care during COVID-19 indicates significant TB service disruptions in the overall population. The finding that incarceration at time of diagnosis was associated with treatment success is plausible in Peru given increased screening and stricter treatment monitoring in prisons. Funding: Canadian Institutes of Health Research (Funding Reference Number: 179418) .

Detection of thermotolerant coliforms and SARS-CoV-2 RNA in sewage and recreational waters in the Ecuadorian coast: A call for improving water quality regulation.

Wastewater surveillance represents an alternative approach to regulating contamination and the early detection of infectious agents and outbreaks of diseases of public health importance. This study evaluated domestic wastewater effects on recreational waters in estuarine and seawater bodies in Guayas and Santa Elena provinces in Ecuador, South America. Fecal indicator bacteria (thermotolerant coliforms) served as key indicators for evaluation. Physical, chemical, and microbiological quality markers following the Ecuadorian environmental quality standard and the discharge of effluents to the water resource were analyzed. Samples were collected from 44 coastal sites and 2 oxidation lagoons during the dry and rainy seasons of 2020 and 2021, respectively. SARS-CoV-2 RNA was detected in samples with higher E. coli concentrations using reverse transcription quantitative PCR to detect the genes N and ORF1ab. All samples analyzed for SARS-CoV-2 showed Ct ˂ 40 for at least one gene. Four samples showed at least 20 genome copies of gene N per reaction. These were at an artisanal fishing port, an estuarine area (Palmar), a recreational bay, and an oxidation lagoon. A moderate correlation was found between SARS-CoV-2 RNA, thermotolerant coliform and E. coli (p-value ≤ 0.0037), and a strong and positive correlation between thermotolerant coliform and E. coli. (p-value ≤ 0.00001), highlighting the utility of these established parameters as a proxy of the virus. Significant differences were found in the concentrations of thermotolerant coliforms between seasons (p-value = 0.016) and sites (p-value = 0.005). The highest levels of coliforms were found in the dry season (63000 MPN/100 mL) in Anconcito and during the rainy season (14000 MPN/100 mL) at Esterillo in Playas County. It is recommended that the decentralized autonomous governments of the surveyed provinces in Ecuador implement urgent corrective actions and establish medium-term mechanisms to minimize a potential contamination route. Additional parameters must be included in the monitoring, such as Enterococcus and intestinal parasites, due to their public health implications. In the oxidation lagoons, maintenance actions must be carried out, including the dissolution of sediments, an increase in water retention times, and in situ treatment of the sludge, to improve the system's performance.

Original article: novelty of Canadian manufacture nasopharyngeal swabs for collection of samples being tested for SARS-CoV-2 in a pandemic setting.

Objectives: The COVID-19 pandemic caused a global shortage of nasopharyngeal (NP) swabs, required for RT-PCR testing. Canadian manufacturers were contacted to share NP swab innovations. The primary objective was to determine whether novel NP test swabs were comparable to commercially available swabs regarding user characteristics, ability to collect a specimen, and diagnostic performance using RT-PCR testing. Methods: Participants were randomized by swab (test/control) and nostril (left/right). A calculated positive percent agreement ≥90% was considered successful. Mean Ct values of viral genes and housekeeping gene (RNase P) were considered similar if a Ct difference ≤ 2 between control and test group was obtained. There also was a qualitative assessment of swabs usability. Results: 647 participants were enrolled from Huaycan Hospital in Lima, Peru, distributed over 8 NP swabs brands. Seven brands agreed to share their results. There were no statistically significant differences between the test swabs of these 7 brands and control swabs. Conclusion: All the seven brands are comparable to the commercially available flocked swabs used for SARS-CoV-2 regarding test results agreement, ability to collect a specimen, and user characteristics.

Challenges in the management of depressive disorders comorbid with tuberculosis and type 2 diabetes.

PURPOSE OF REVIEW: The aim of this study was to address the most relevant diagnostic and therapeutic challenges in the management of depressive disorders among patients with diabetes mellitus and tuberculosis (TB). RECENT FINDINGS: Depressive disorder, diabetes mellitus and TB are considered important contributors to the global burden of diseases with an emphasis on developing countries. Depressive disorder increases the chance of negative outcomes during the treatment of both diabetes mellitus and TB, while biological and adaptive changes due to diabetes mellitus and TB increase in turn the chance of depressive disorder. SUMMARY: In this review, we present major challenges in the management of depressive disorder among patients with TB and diabetes mellitus, from detection and clinical diagnosis using appropriate diagnostic tools, to selecting the best psychotherapeutic and/or pharmacological intervention, considering the potential, adverse events and interactions due to potential polypharmacy.

Improving measurement of tuberculosis care cascades to enhance people-centred care.

Care cascades represent the proportion of people reaching milestones in care for a disease and are widely used to track progress towards global targets for HIV and other diseases. Despite recent progress in estimating care cascades for tuberculosis (TB) disease, they have not been routinely applied at national and subnational levels, representing a lost opportunity for public health impact. As researchers who have estimated TB care cascades in high-incidence countries (India, Madagascar, Nigeria, Peru, South Africa, and Zambia), we describe the utility of care cascades and identify measurement challenges, including the lack of population-based disease burden data and electronic data capture, the under-reporting of people with TB navigating fragmented and privatised health systems, the heterogeneity of TB tests, and the lack of post-treatment follow-up. We outline an agenda for rectifying these gaps and argue that improving care cascade measurement is crucial to enhancing people-centred care and achieving the End TB goals.

Diagnostic performance of four lateral flow immunoassays for COVID-19 antibodies in Peruvian population.

Serological assays have been used in seroprevalence studies to inform the dynamics of COVID-19. Lateral flow immunoassay (LFIA) tests are a very practical technology to use for this objective; however, one of their challenges may be variable diagnostic performance. Given the numerous available LFIA tests, evaluation of their accuracy is critical before real-world implementation. We performed a retrospective diagnostic evaluation study to independently determine the diagnostic accuracy of 4 different antibody-detection LFIA tests: Now Check (Bionote), CareStart (Access bio), Covid-19 BSS (Biosynex) and OnSite (CTK Biotech). The sample panel was comprised of specimens collected and stored in biobanks; specifically, specimens that were RT-PCR positive for SARS-CoV-2 collected at various times throughout the COVID-19 disease course and those that were collected before the pandemic, during 2018 or earlier, from individuals with upper respiratory symptoms but were negative for tuberculosis. Clinical performance (sensitivity and specificity) was analyzed overall, and subset across individual antibody isotypes, and days from symptoms onset. A very high specificity (98% - 100%) was found for all four tests. Overall sensitivity was variable, ranging from 29% [95% CI: 21%-39%] to 64% [95% CI: 54%-73%]. When considering detection of IgM only, the highest sensitivity was 42% [95% CI: 32%-52%], compared to 57% [95% CI: 47%-66%] for IgG only. When the analysis was restricted to at least 15 days since symptom onset, across any isotype, the sensitivity reached 90% for all four brands. All four LFIA tests proved effective for identifying COVID-19 antibodies when two conditions were met: 1) at least 15 days have elapsed since symptom onset and 2) a sample is considered positive when either IgM or IgG is present. With these considerations, the use of this assays could help in seroprevalence studies or further exploration of its potential uses.

Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study.

OBJECTIVES: Protein intake impacts on nutritional status and may determine the recurrence of hepatic encephalopathy (HE). A low-protein diet has been considered the standard treatment after an episode of HE, while branched-chain amino acids (BCAA) have been shown to improve minimal HE. We performed a study to investigate the long-term effects of supplementing a protein-controlled diet with BCAA. METHODS: A randomized, double-blind, multicenter study that included 116 patients with cirrhosis and a previous episode of HE was conducted in four tertiary care hospitals. All patients received a standard diet of 35 kcal/kg per day and 0.7 g of proteins/kg per day and a supplement of 30 g of BCAA (BCAA group) or maltodextrin (MDX group) during 56 weeks. RESULTS: The actuarial risk of remaining free of HE did not differ between groups (BCAA=47%, MDX=34%, P=0.274), but patients in the BCAA group exhibited a better outcome on two neuropsychological tests and an increase in the mid-arm muscle circumference. Recurrence was associated with low plasma albumin at baseline and a decrease in sodium and an increase in creatinine during follow-up. Patients with recurrence of HE exhibited a lack of improvement in global cognitive function. CONCLUSIONS: Diet supplementation with BCAA after an episode of HE does not decrease recurrence of HE. However, supplementation with BCAA improves minimal HE and muscle mass. Identification of risk factors for recurrence of HE may allow the development of new preventive therapies that could decrease the neuropsychological sequelae of repeated episodes of HE.

A new insight into the cellular mechanisms of envenomation: Elucidating the role of extracellular vesicles in Loxoscelism.

Envenomation by the Loxosceles genus spiders is a recurring health issue worldwide and specially in the Americas. The physiopathology of the envenomation is tightly associated to the venom's rich toxin composition, able to produce a local dermonecrotic lesion that can evolve systemically and if worsened, might result in multiple organ failure and lethality. The cellular and molecular mechanisms involved with the physiopathology of Loxoscelism are not completely understood, however, the venom's Phospholipases D (PLDs) are known to trigger membrane injury in various cell types. Here, we report for the first time the Loxosceles venom's ability to stimulate the production of extracellular vesicles (EVs) in various human cell lineages. Components of the Loxosceles venom were also detectable in the cargo of these vesicles, suggesting that they may be implicated in the process of extracellular venom release. EVs from venom treated cells exhibited phospholipase D activity and were able to induce in vitro hemolysis in human red blood cells and alter the HEK cell membranes' permeability. Nonetheless, the PLD activity was inhibited when an anti-venom PLDs monoclonal antibody was co-administered with the whole venom. In summary, our findings shed new light on the mechanisms underlying cellular events in the context of loxoscelism and suggest a crucial role of EVs in the process of envenomation.

Evaluation of Resting Energy Expenditure in Subjects with Severe Obesity and Its Evolution After Bariatric Surgery.

PURPOSE: One major determinant of weight loss is resting energy expenditure (REE). However, data regarding REE is scarce in patients with severe obesity (SO)-BMI>50kg/m2. Most studies used equation in order to estimate REE and not indirect calorimetry (IC) (gold standard). Additionally, there is no reliable data on the impact of bariatric surgery (BS) on REE. OBJECTIVES: (a) To evaluate the REE in patients with SO; (b) to compare REE measured by IC (mREE) to that calculated by Mifflin St-Jeor equation (eREE); (c) to evaluate the impact of BS on REE and the relationship with evolution post-BS. MATERIAL AND METHODS: Single-center observational study including consecutive patients with SO between January 2010 and December 2015, candidates for BS. mREE was determined at baseline, and 1 and 12 months post-BS by IC, using a Vmax metabolic monitor. RESULTS: Thirty-nine patients were included: mean age 46.5±11.77 years, 64.1%women. Preoperative mREE was 2320.38±750.81 kcal/day. One month post-BS, the mREE significantly decreased (1537.6 ± 117.46 kcal/day, p = 0.023) and remained unchanged at 12 months (1526.00 ± 123.35 kcal/day; p =0.682). Reduction in mREE after the BS was a predictor of reaching successful weight loss (nadir) and weight regain (5 years follow-up) (AUCROC of 0.841 (95%CI [0.655-0.909], p=0.032) and AUCROC of 0.855 (95% CI [0.639-0.901]), p= 0.027, respectively). eREE was not valid to identify these changes. CONCLUSION: In patients with SO, a significant reduction of mREE occurs 1 month post-BS, unchanged at 12 months, representing the major conditioning of successful weight loss and maintenance post-BS.

Basiliximab vs. limited-dose daclizumab (2 mg/kg) administered in single or two separated doses in kidney transplantation.

INTRODUCTION: Addition of anti-IL2r monoclonal antibodies (chimeric or humanized) for induction therapy has reduced the frequency of acute rejection (AR). This study compares the impact of type and dosage of induction therapy on frequency of acute rejection and on renal function during the first year post-transplant. PATIENTS AND METHODS: Comparative retrospective study. Kidney transplant recipients (KTR) were divided in three groups according to induction therapy, as follows: (1) Basiliximab in two 20 mg doses, (2) Daclizumab 2 mg/kg in one dose, and (3) Daclizumab 2 mg/kg divided in two doses (1 mg/kg each). Groups were paired for age, sex, number of shared haplotypes, and previous transplant history. Primary endpoints were AR episodes, time to first AR, graft loss, and death. Secondary endpoints were SCr (at 3, 6, 9 and 12 months), frequency and type of infection, and cost. RESULTS: There were no baseline differences between groups. Twenty one patients were included in each group. The incidence of AR was similar: 14.2% in group 1, and 9.5% for groups 2 and 3. Two deaths were reported, one in group 1 and another in group 2. Mean SCr was similar between groups. Incidence of infection was 6, 5, and 7 in groups 1 to 3, respectively without a significant difference. The cost was higher in group 1 (p < 0.001). CONCLUSION: Low dose Daclizumab in one or two doses is equally effective and safe as basiliximab at 12-month follow-up, with inferior cost.

[Basic concepts on 18F-FDG PET/CT: definitions and normal variants]. / Conceptos básicos del 18F-FDG PET/CT. Definición y variantes normales.

The PET/CT (positron emission tomography with multislice helical computed tomography), is nowadays one of the leader imaging diagnostic tools in medicine. This technology has been present in Mexico since the last three years. Although the physical principles of PET has been known for more than 30 years, it has been the introduction of PET/CT what let the acquisition and post processing of fused PET/CT images currently used in imaging diagnosis in clinical medicine. These fused PET/CT images allow an accurate localization of the abnormal fluorine-18 Fluorodeoxyglucose (18F-FDG) uptake, which can be related to inflammation or neoplastic processes. This article presents a brief review of the fundamentals of PET/CT, the basic physics principles and examples of normal variants of the 18F-FDG uptake that are not associated with a neoplastic entity.

Oncogenic mutations in IKKß function through global changes induced by K63-linked ubiquitination and result in autocrine stimulation.

Mutations at position K171 in the kinase activation loop of Inhibitor of κB kinase beta (IKKß) occur in multiple myeloma, spleen marginal zone lymphoma and mantle cell lymphoma. Previously, we demonstrated that these result in constitutive kinase activation and stimulate Signal Transducer and Activator of Transcription 3 (STAT3). This work also identified K147 as a site of K63-linked regulatory ubiquitination required for activation of signaling pathways. We now present a more detailed analysis of ubiquitination sites together with a comprehensive examination of the signaling pathways activated by IKKß K171E mutants. Downstream activation of STAT3 is dependent upon the activity of: UBE2N, the E2 ubiquitin ligase involved in K63-linked ubiquitination; TAK1 (MAP3K7), or TGFß Activated Kinase, which forms a complex required for NFκB activation; JAK kinases, involved proximally in the phosphorylation of STAT transcription factors in response to inflammatory cytokines; and gp130, or IL-6 Receptor Subunit Beta which, upon binding IL-6 or other specific cytokines, undergoes homodimerization leading to activation of associated JAKs, resulting in STAT activation. We further demonstrate, using an IL-6-responsive cell line, that IKKß K171E mutants stimulate the release of IL-6 activity into conditioned media. These results show that IKKß K171E mutants trigger an autocrine loop in which IL-6 is secreted and binds to the IL-6 receptor complex gp130, resulting in JAK activation. Lastly, by examining the differential abundance of proteins associated with K63-only-ubiquitinated IKKß K171E, proteomic analysis demonstrates the global activation of proliferative responses. As cancers harboring K171-mutated IKKß are likely to also exhibit activated STAT3 and p44/42 MAPK (Erk1/2), this suggests the possibility of using MAPK (Erk1/2) and JAK inhibitors, or specific ubiquitination inhibitors. K63-linked ubiquitination occurs in other kinases at sites homologous to K147 in IKKß, including K578 in BRAF V600E, which serves as an oncogenic driver in melanoma and other cancers.

Quality of life in cirrhosis is related to potentially treatable factors.

OBJECTIVE: Improvement of prognosis and availability of diverse therapeutic options for complications of advanced liver disease highlight the importance of health-related quality of life (HRQOL) in cirrhosis. The aim of this study was to identify factors that influence HRQOL and may be potentially treatable in patients with cirrhosis. METHODS: HRQOL was measured in 212 outpatients with cirrhosis using a generic questionnaire (Medical Outcomes Study Form, SF-36) and a liver-specific questionnaire (Chronic Liver Disease Questionnaire, CLDQ). All patients underwent a systematic clinical and neuropsychological assessment. Independent factors associated with poor HRQOL were identified by multiple linear regression. RESULTS: HRQOL scores exhibited by patients were: global CLDQ: 4.8+/-1.2; Physical Component Score of SF-36: 38.5+/-10.7; Mental Component Score of SF-36: 45.3+/-14.3. The independent variables for global CLDQ were female sex, nonalcoholic etiology, current ascites, and a decrease in albumin (R = 0.22). For Physical Component Score of SF-36, the independent variables were prior hepatic encephalopathy, current ascites, and a decrease in hemoglobin (R = 0.22). For Mental Component Score of SF-36, the independent variables were nonalcoholic etiology, the Grooved Pegboard test, and a decrease in hemoglobin (R = 0.14). CONCLUSION: Several clinical variables, potentially treatable, may alter particular aspects of HRQOL. Correction of ascites, hypoalbuminemia, minimal hepatic encephalopathy, and anemia may cause a positive impact on HRQOL of patients with cirrhosis.

Conceptos básicos del 18F-FDG PET/CT: definición y variantes normales / Basic concepts on 18F-FDG PET/CT: definitions and normal variants

La tomografía por emisión de positrones con tomografía multicorte (PET/CT) constituye uno de los métodos de diagnóstico por imagen más modernos; esta tecnología llegó a nuestro país en los tres últimos años. Aunque los principios físicos del PET datan de hace más de 30 años, la fusión de las imágenes con la tomografía multicorte en el posprocesamiento, ha marcado un hito en la detección de estructuras anatómicas con una captación anormal de radiofármacos que puede estar relacionada con inflamación o neoplasia. Este artículo presenta una revisión breve de los principios básicos de PET/CT, la física de la generación de un radiofármaco, la adquisición de la imagen, y sobre todo, se muestran ejemplos de las “variantes normales” que presentan una captación aumentada de 18F-FDG, y que no están relacionadas a un proceso neoplásico.

The PET/CT (positron emission tomography with multislice helical computed tomography), is nowadays one of the leader imaging diagnostic tools in medicine. This technology has been present in Mexico since the last three years. Although the physical principles of PET has been known for more than 30 years, it has been the introduction of PET/CT what let the acquisition and post processing of fused PET/CT images currently used in imaging diagnosis in clinical medicine. These fused PET/CT images allow an accurate localization of the abnormal fluorine-18 Fluorodeoxyglucose (18F-FDG) uptake, which can be related to inflammation or neoplastic processes. This article presents a brief review of the fundamentals of PET/CT, the basic physics principles and examples of normal variants of the 18F-FDG uptake that are not associated with a neoplastic entity.

Mediciones craneales en el recién nacido: estudio conjunto con otras dimensiones en la región central de Cuba / Cranial measurement of the newborn: joint study on other dimensions of a sample taken from the central region of Cuba

Se tomó una muestra de 300 recién nacidos de ambos sexos en el Hospital Ginecobstétrico de Santa Clara en el año 1987 para estudiar mediciones de peso, longitud supina, circunferencias cefálica y torácica y diámetros craneales, así como la edad de la madre. Fueron analizadas todas las variables según el sexo del neonato; se determinó la correlación entre ellas y se encontró que las mayores relaciones existían entre el peso con las circunferencias torácica y cefálica y longitud supina. Se halló diferencias altamente significativas en el peso, longitud supina, circunferencia cefálica y diámetro anteroposterior y transverso de la cabeza y significativas, en la circunferencia torácica. Los recién nacidos fueron clasificados de acuerdo con los índices craneales calculados, en los que hubo un predominio de los tipos mesocéfalo, ortocéfalo y tapeinocéfalo