Outcomes for people with TB by disease severity at presentation.

There is substantial heterogeneity in disease presentation for individuals with TB disease, which may correlate with disease outcomes. We estimated disease outcomes by disease severity at presentation among individuals with TB during the pre-chemotherapy era.We extracted data on people with TB enrolled between 1917 and 1948 in the USA, stratified by three disease severity categories at presentation using the U.S. National Tuberculosis Association diagnostic criteria. These criteria were based largely on radiographic findings ("minimal", "moderately advanced", and "far advanced"). We used Bayesian parametric survival analysis to model the survival distribution overall, and by disease severity and Bayesian logistic regression to estimate the severity-level specific natural recovery odds within 3 years.People with minimal TB at presentation had a 2% (95% CrI 0-11%) probability of TB death within 5 years vs. 40% (95% CrI 15-68) for those with far advanced disease. Individuals with minimal disease had 13.62 times the odds (95% CrI 9.87-19.10) of natural recovery within 3 years vs. those with far advanced disease.Mortality and natural recovery vary by disease severity at presentation. This supports continued work to evaluate individualized (e.g., shortened or longer) regimens based on disease severity at presentation, identified using radiography..

Clinical impact of capsule endoscopy on patients with suspected small bowel bleeding: Experience at a highly specialized hospital in Colombia.

INTRODUCTION AND AIMS: Capsule endoscopy is part of the diagnostic approach to patients with suspected small bowel bleeding and data on its clinical impact are still limited in developing countries. The primary aim of the present study was to determine its impact on subsequent diagnostic and therapeutic decisions. MATERIAL AND METHODS: A retrospective study was conducted that included all the patients that underwent capsule endoscopy with the PillCam™ SB 3 Capsule system due to suspected small bowel bleeding treated at the Hospital Universitario Fundación Valle del Lili between January 2011 and December 2020. RESULTS: A total of 158 patients met the inclusion criteria. Mean patient age was 63 years (interquartile range [IQR], 52-74), 53.6% of the patients were women, and high blood pressure was the most frequent comorbidity (43.7%). The main indication was overt bleeding (58.2%). Of all the capsule endoscopies carried out, 63.9% showed lesions that were potentially responsible for bleeding. Medical or surgical treatment was indicated in 63.3% of the case total. Rebleeding at 6 months occurred in 15 patients and there were 2 deaths due to gastrointestinal bleeding at 6 months. CONCLUSIONS: Capsule endoscopy has a high impact on patients with suspected small bowel bleeding, with respect to clinical decision-making, as well as rebleeding, hospitalization, and mortality outcomes. The positivity rate of lesions potentially responsible for bleeding was similar to that reported in developed countries.

Survival of people with untreated TB: effects of time, geography and setting.

BACKGROUND: An estimated 40% of people who developed TB in 2021 were not diagnosed or treated. Pre-chemotherapy era data are a rich resource on survival of people with untreated TB. We aimed to identify heterogeneities in these data to inform their more precise use.METHODS: We extracted survival data from pre-chemotherapy era papers reporting TB-specific mortality and/or natural recovery data. We used Bayesian parametric survival analysis to model the survival distribution, stratifying by geography (North America vs. Europe), time (pre-1930 vs. post-1930), and setting (sanitoria vs. non-sanitoria).RESULTS: We found 12 studies with TB-specific mortality data. Ten-year survival was 69% in North America (95% CI 54-81) and 36% in Europe (95% CI 10-71). Only 38% (95% CI 18-63) of non-sanitorium individuals survived to 10 years compared to 69% (95% CI 41-87) of sanitoria/hospitalized patients. There were no significant differences between people diagnosed pre-1930 and post-1930 (5-year survival pre-1930: 65%, 95% CI 44-88 vs. post-1930: 72%, 95% CI 41-94).CONCLUSIONS: Mortality and natural recovery risks vary substantially by location and setting. These heterogeneities need to be considered when using pre-chemotherapy data to make inferences about expected survival of people with undiagnosed TB.

Finding Nivo: A Case Report of 2 Forms of Nivolumab-Induced Liver Injury in an Allograft Liver in the Immediate Post-Transplant Period.

Recent reports have emerged regarding the utilization of checkpoint inhibitors for downstaging hepatocellular carcinoma before liver transplantation. Early post-transplant acute cellular rejection has rarely led to graft loss. We report the first case of 2 forms of nivolumab-associated liver injury on biopsy of the allograft organ in a single patient who received nivolumab for cancer downstaging before liver transplantation: 1. mild acute cellular rejection according to Risk Analysis Index scoring and 2. zone 3 inflammation and apoptosis consistent with a more classic drug-induced liver injury pattern. This case not only adds further evidence about the risk for rejection post-transplant, but sheds light on other injuries checkpoint inhibitors can cause to the allograft.

Biomaterials Used for Periodontal Disease Treatment: Focusing on Immunomodulatory Properties.

The growing use of biomaterials with different therapeutic purposes increases the need for their physiological understanding as well as to seek its integration with the human body. Chronic inflammatory local pathologies, generally associated with infectious or autoimmunity processes, have been a current therapeutic target due to the difficulty in their treatment. The recent development of biomaterials with immunomodulatory capacity would then become one of the possible strategies for their management in local pathologies, by intervening in situ, without generating alterations in the systemic immune response. The treatment of periodontal disease as an inflammatory entity has involved the use of different approaches and biomaterials. There is no conclusive, high evidence about the use of these biomaterials in the regeneration of periodontitis sequelae, so the profession keeps looking for other different strategies. The use of biomaterials with immunomodulatory properties could be one, with a promising future. This review of the literature summarizes the scientific evidence about biomaterials used in the treatment of periodontal disease.

A facile synthesis of CuBi2O4 hierarchical dumbbell-shaped nanorod cluster: a promising photocatalyst for the degradation of caffeic acid.

The present study reports on the synthesis of Cu-bismuth oxide (CuBi2O4)-based nanorods by using a simple co-precipitation method for the photocatalytic degradation of caffeic acid (CA). The incorporation of Cu metal ions during the synthesis of CuBi2O4 nanorods might be advantageous to avoid the aggregation and control the leach out of metal ions. The calculated bandgap values of ~ 1.04, 1.02, and 0.94 eV were observed for CuBi2O4 with different amounts of Cu 1.0, 0.50, and 0.25 g, respectively. Varying the quantity of Cu metal ions easily tuned the bandgap value within the CuBi2O4-based nanorods. However, a further decrease in the bandgap value increased the recombination rate, and the less photocatalyst performance was observed. The CA degradation could be explained based on the species distribution. The CA pKa was mainly located between pKa1 and pKa2 of 4.43 and 8.6, respectively. The Cu within the CuBi2O4-based nanorods changed the electronic properties and the antibacterial ability. Therefore, the synthesized CuBi2O4-based nanorod cluster might be a promising material for the photocatalytic degradation of CA.

Early mortality during rifampicin-resistant TB treatment.

BACKGROUND: Data suggest that treatment with newer TB drugs (linezolid [LZD], bedaquiline [BDQ] and delamanid [DLM]), used in Khayelitsha, South Africa, since 2012, reduces mortality due to rifampicin-resistant TB (RR-TB).METHODS: This was a retrospective cohort study to assess 6-month mortality among RR-TB patients diagnosed between 2008 and 2019.RESULTS: By 6 months, 236/2,008 (12%) patients died; 12% (78/651) among those diagnosed in 2008-2011, and respectively 8% (49/619) and 15% (109/738) with and without LZD/BDQ/DLM in 2012-2019. Multivariable analysis showed a small, non-significant mortality reduction with LZD/BDQ/DLM use compared to the 2008-2011 period (aOR 0.79, 95% CI 0.5-1.2). Inpatient treatment initiation (aOR 3.2, 95% CI 2.4-4.4), fluoroquinolone (FQ) resistance (aOR 2.7, 95% CI 1.8-4.2) and female sex (aOR 1.5, 95% CI 1.1-2.0) were also associated with mortality. When restricted to 2012-2019, use of LZD/BDQ/DLM was associated with lower mortality (aOR 0.58, 95% CI 0.39-0.87).CONCLUSIONS: While LZD/BDQ/DLM reduced 6-month mortality between 2012 and 2019, there was no significant effect overall. These findings may be due to initially restricted LZD/BDQ/DLM use for those with high-level resistance or treatment failure. Additional contributors include increased treatment initiation among individuals who would have otherwise died before treatment due to universal drug susceptibility testing from 2012, an effect that also likely contributed to higher mortality among females (survival through to care-seeking).

Postoperative complications and waiting time for surgical intervention after radiologically guided drainage of intra-abdominal abscess in patients with Crohn's disease.

BACKGROUND: In patients with active Crohn's disease (CD), treatment of intra-abdominal abscess usually comprises antibiotics and radiologically guided percutaneous drainage (PD) preceding surgery. The aim of this study was to investigate the risk of postoperative complications and identify the optimal time interval for surgical intervention after PD. METHODS: A multicentre, international, retrospective cohort study was carried out. Details of patients with diagnosis of CD who underwent ultrasonography- or CT-guided PD were retrieved from hospital records using international classification of disease (ICD-10) diagnosis code for CD combined with procedure code for PD. Clinical variables were retrieved and the following outcomes were measured: 30-day postoperative overall complications, intra-abdominal septic complications, unplanned intraoperative adverse events, surgical-site infections, sepsis and pathological postoperative ileus, in addition to abscess recurrence. Patients were categorized into three groups according to the length of the interval from PD to surgery (1-14 days, 15-30 days and more than 30 days) for comparison of outcomes. RESULTS: The cohort comprised 335 CD patients with PD followed by surgery. Median age was 33 (i.q.r. 24-44) years, 152 (45.4 per cent) were females, and median disease duration was 9 (i.q.r. 3.6-15) years. Overall, the 30-day postoperative complications rate was 32.2 per cent and the mortality rate was 1.5 per cent. After adjustment for co-variables, older age (odds ratio 1.03 (95 per cent c.i. 1.01 to 1.06), P < 0.012), residual abscess after PD (odds ratio 0.374 (95 per cent c.i. 0.19 to 0.74), P < 0.014), smoking (odds ratio 1.89 (95 per cent c.i. 1.01 to 3.53), P = 0.049) and low serum albumin concentration (odds ratio 0.921 (95 per cent c.i. 0.89 to 0.96), P < 0.001) were associated with higher rates of postoperative complications. A short waiting interval, less than 2 weeks after PD, was associated with a high incidence of abscess recurrence (odds ratio 0.59 (95 per cent c.i. 0.36 to 0.96), P = 0.042). CONCLUSION: Smoking, low serum albumin concentration and older age were significantly associated with postoperative complications. An interval of at least 2 weeks after successful PD correlated with reduced risk of abscess recurrence.

A novel bimetallic (Fe/Bi)-povidone-iodine micro-flowers composite for photocatalytic and antibacterial applications.

The present work describes the synthesis of polyvinylpyrrolidone (PVP) assisted Fe-BiOI based Fe/Bi-povidone­iodine (Fe/Bi-P-I) micro-flowers based composite and its photocatalytic and antibacterial applications. The Fe/Bi-P-I micro-flowers-based composite material was synthesized using a simple co-precipitation method. The prepared Fe/Bi-P-I micro-flowers-based composite materials were characterized using various characterization techniques and tested against photocatalytic degradation of rhodamine B (RhB) dye and antibacterial analysis. The PVP or povidone­iodine provides more exposure of reactive sites and oxygen vacancies, which leads to a high separation rate of photoinduced charge carriers, and migration, thereby 100% of photodegradation efficiency at 1 mg/L initial concentration of RhB dye towards the synthesized P-Fe-BiOI based micro-flowers composite. Interestingly, Povidone-Iodine in Fe/Bi-P-I micro-flowers-based composite might be advantageous for antimicrobial activity against both gram-negative (E. coli), and gram-positive (S. aureus) bacterial strains. Therefore, the prepared Fe/Bi-P-I micro-flowers-based composite improved both photocatalytic degradation of organic pollutants as well as high antimicrobial activity. The method of synthesizing the Bi/Fe-P-I micro flower composite in the present study is novel, facile, and economically viable.

Bimetal (Fe/Zn) doped BiOI photocatalyst: An effective photodegradation of tetracycline and bacteria.

Tetracycline (TC) is one of the most commonly used broad-spectrum antibiotics to treat the bacterial infection. TC antibiotics enter into the environment because of partial metabolism in the humans and animals, thereby increasing the environmental toxicity. Therefore, it is highly needed to treat TC antibiotics from the water system. In this aspect, the present work focus on the synthesis of Fe and Zn (bimetal) incorporated with different concentrations into the bismuth-oxy-iodide (Fe/Zn-BiOI) based photocatalyst materials. The synthesized Fe/Zn-BiOI was tested against photocatalytic degradation of TC antibiotics and bacteria. The band gap value of the synthesized Fe/Zn-BiOI was calculated ~2.19 eV. The incorporation of the Fe and Zn metals within the BiOI aided advantages that increased the reactive sites, oxygen defects, photon adsorption, production of hydroxyl radicals, and decrease the recombination rate, thereby high photo-degradation ability. The maximum degradation of ~83% was observed using Fe/Zn-BiOI-1-1 at 10 mg/L of TC antibiotics concentration. Moreover, ~98% of degradation was observed at pH~10 of the TC antibiotics. The photo-activity against bacteria of the Fe/Zn-BiOI was also determined. The data suggested that the synthesized Fe/Zn-BiOI based photocatalyst materials effectively inhibited the bacterial strains. Therefore, Fe/Zn-BiOI based photocatalyst materials might be promising materials that effectively degrade TC antibiotics as well as bacteria.

Strategic Doping Approach of the Fe-BiOI Microstructure: An Improved Photodegradation Efficiency of Tetracycline.

The present study describes the strategic doping of Fe metal ions into a BiOI microstructure using ex situ and in situ processes to synthesize a Fe-BiOI microstructure and their effect on photocatalytic degradation of tetracycline (TC). The data suggested that in situ Fe-BiOI (Fe-BiOI-In) has superior performance compared to ex situ Fe-BiOI (Fe-BiOI-Ex) due to the uniform dispersion of Fe within the Fe-BiOI material. Calculated bandgaps ∼1.8, ∼1.5, and 2.4 eV were observed for BiOI (without Fe), Fe-BiOI-In, and Fe-BiOI-Ex, respectively. Interestingly, Fe incorporation within BiOI might decrease the bandgap in Fe-BiOI-In due to the uniform distribution of metal ions, whereas increasing the bandgap in Fe-BiOI-Ex attributed to nonuniform distribution or agglomeration of metal ions. The uniform dispersion of Fe within Fe-BiOI modulates electronic properties as well as increases the exposure of Fe ions with TC, thereby higher degradation efficiency of TC. The in situ Fe-BiOI material shows 67 and 100% degradation of TC at 10 and 1 mg/L, respectively. The TC degradation was also found to be pH-dependent; when increasing the pH value up to 10, 94% degradation was achieved at 10 mg/L within 60 min of solar irradiation. The analysis was also performed over BiOI, which proves that Fe has a profound effect on TC degradation as Fe(II) tends to trigger oxidation-reduction by utilizing the chelate formation tendency of TC. Therefore, the prepared Fe-BiOI-In has the potential ability to degrade pharmaceutical compounds, especially, TC from wastewater.

Avoided crossings and dynamical tunneling close to excited-state quantum phase transitions.

Using the Wehrl entropy, we study the delocalization in phase space of energy eigenstates in the vicinity of avoided crossings in the Lipkin-Meshkov-Glick model. These avoided crossings, appearing at intermediate energies in a certain parameter region of the model, originate classically from pairs of trajectories lying in different phase-space regions which, contrary to the low-energy regime, are not connected by the discrete parity symmetry of the model. As coupling parameters are varied, a sudden increase of the Wehrl entropy is observed for eigenstates participating in avoided crossings that are close to the critical energy of the excited-state quantum phase transition. This allows us to detect when an avoided crossing is accompanied by a superposition of the pair of classical trajectories in the Husimi function of eigenstates. This superposition yields an enhancement of dynamical tunneling, which is observed by considering initial Bloch states that evolve partially into the partner region of the paired classical trajectories, thus breaking the quantum-classical correspondence in the evolution of observables.

Barriers and facilitators to early access of bedaquiline and delamanid for MDR-TB: a mixed-methods study.

SETTING: Phase II trials for bedaquiline (BDQ) and delamanid (DLM) were completed by 2011 and the drugs were approved by stringent regulatory authorities for the treatment of multidrug-resistant tuberculosis (MDR-TB) between 2012 and 2014. Manufacturers established 'early access' mechanisms to provide drugs before local registration. OBJECTIVE: To inform improvements in early access, we explored experiences of providers and advocates in accessing BDQ and DLM before the end of 2015 using a mixed-methods design. DESIGN: We examined barriers and facilitators to early access through an electronic survey. Barriers and facilitators were classified as occurring at the manufacturer- or country-level. We identified themes using inductive content analysis and illustrated themes through case studies. RESULTS: We analysed 41 survey responses from 36 respondents reporting on 22 countries; early access was attempted in 30 (73%) survey responses. Eligibility restrictions (11/30, 37%) and complicated and slow processes (8/30, 27%) were manufacturer-level barriers; access to companion drugs (10, 33%) and importation difficulties (4, 13%) were country-level barriers. Previous experience with manufacturer (3/30, 10%) and country processes (2/30, 7%) facilitated access. Eight case studies show the human impact of barriers and facilitators. CONCLUSION: Manufacturers and countries should develop transparent processes to permit early access, particularly for diseases that largely affect the poor, such as MDR-TB. Developers should plan for this need and rapidly register drugs with proven benefit, prioritizing high-burden settings.

Effective use of mesenchymal stem cells in human skin substitutes generated by tissue engineering.

Mesenchymal stem cells (MSCs) can differentiate toward epithelial cells and may be used as an alternative source for generation of heterotypical artificial human skin substitutes, thus, enhancing their development and translation potential to the clinic. The present study aimed at comparing four types of heterotypical human bioengineered skin generated using MSCs as an alternative epithelial cell source. Adipose-tissue-derived stem cells (ADSCs), dental pulp stem cells (DPSCs), Wharton's jelly stem cells (WJSCs) and bone marrow stem cells (BMSCs) were used for epidermal regeneration on top of dermal skin substitutes. Heterotypic human skin substitutes were evaluated before and after implantation in immune-deficient athymic mice for 30 d. Histological and genetic studies were performed to evaluate extracellular matrix synthesis, epidermal differentiation and human leukocyte antigen (HLA) molecule expression. The four cell types differentiated into keratinocytes, as shown by the expression of cytokeratin 10 and filaggrin 30 d post-grafting; also, they induced dermal fibroblasts responsible for the synthesis of extracellular fibrillar and non-fibrillar components, in a similar way among each other. WJSCs and BMSCs showed higher expression of cytokeratin 10 and filaggrin, suggesting these cells were more prone to epidermal regeneration. The absence of HLA molecules, even when the epithelial layer was differentiated, supports the future clinical use of these substitutes - especially ADSCs, DPSCs and WJSCs - with low rejection risk. MSCs allowed the generation of bioengineered human skin substitutes with potential clinical usefulness. According to their epidermal differentiation potential and lack of HLA antigens, WJSCs should preferentially be used.

The Medical Oncology resident mentor: situation and workload.

PURPOSE: The Spanish Society for Medical Oncology (SEOM, for its acronym in Spanish) and the National Commission for the Specialty of Medical Oncology seek to highlight the important workload and unrecognized dedication entailed in working as a Medical Oncology (MO) resident mentor, as well as its relevance for the quality of teaching units and the future of the specialty. MATERIALS AND METHODS: The current situation and opinion regarding the activity of MO resident mentors was analyzed by reviewing the standing national and autonomic community regulations and via an online survey targeting mentors, residents, and physicians who are not MO mentors. The project was supervised by a specially designated group that agreed on a proposal containing recommendations for improvement. RESULTS: Of the MO mentors, 90% stated that they did not have enough time to perform their mentoring duties. An estimated 172 h/year on average was dedicated to mentoring, which represents 10.1% of the total time. MO mentors dedicate an average of 6.9 h/month to these duties outside their workday. Forty-five percent of the mentors feel that their role is scantly recognized, if at all. CONCLUSIONS: The study reveals the substantial dedication and growing complexity of MO resident mentoring. A series of recommendations are issued to improve the conditions in which it is carried out, including the design of systems that adapt to the professional activity in those departments that have time set aside for mentoring tasks.