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Background: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19., Methods: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both., Results: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53)., Conclusions: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2023.) more...

Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis ( Mtb -Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb -Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Amiano, Pellegrini, Morelli, Martinena, Rolandelli, Castello, Casco, Ciallella, de Casado, Armitano, Stupka, Gallego, Palmero, García and Tateosian.) more...

Th17 lymphocytes, that produce IL17A, IL17F, and IL22, play a crucial role during the immune response against Mycobacterium tuberculosis ( Mtb ) infection. Whereas, the contribution of IL17A in immunity to tuberculosis is usually accepted, the role of IL17F has been scarcely studied so far. The aim of this work was to evaluate the existence of a potential association of the non-synonymous variant rs763780 SNP of the IL17F gene with human tuberculosis. Accordingly, by comparing healthy donors (HD) and tuberculosis patients (TB) populations we demonstrated an association between the C allele of the SNP and the susceptibility to tuberculosis disease in Argentina. Furthermore, we found that peripheral blood mononuclear cells (PBMCs) from individuals with a more effective immune response against Mtb secreted the highest levels of IL17F when stimulated with a lysate of Mtb ( Mtb -Ag). Besides, we evidenced that Mtb -Ag-stimulated PBMCs from HD carrying the C variant of the SNP displayed the lowest IFNG secretion, proliferation index, and SLAM expression as compared to TT carriers. Moreover, Mtb -Ag-stimulated PBMCs from TB carrying the C allele produced the lowest levels of IFNG, the highest level of IL17A, and the minimum proliferation indexes as compared to TT TB, suggesting a relationship between the C allele and tuberculosis severity. In fact, TB carrying the C allele presented a more severe disease, with the highest bacilli burden in sputum. Together, our findings identify the IL17F rs763780 SNP as a biomarker of tuberculosis susceptibility and advanced disease severity in Argentina, suggesting that IL17F could be a critical cytokine in tuberculosis immunity., (Copyright © 2019 Rolandelli, Pellegrini, Hernández Del Pino, Tateosian, Amiano, Morelli, Castello, Casco, Levi, Palmero and García.) more...

Objectives: Extracorporeal shock wave lithotripsy is a minimally invasive therapeutic option for the treatment of renal-ureteral lithiasis. The aim of this study was to analyze the results and complications of shock wave extracorporeal lithotripsy treatment with the Dornier Gemini® Generator EMSE 220f-XXP device in patients with renal and ureteral lithiasis., Material and Methods: Retrospective study including 377 patients with renal or ureteral lithiasis with indication for treatment with extracorporeal shock wave lithotripsy. The following variables were analyzed, age, sex, body mass index, lithiasis size, lithiasis location, presence of urinary diversion, number of lithotripsy sessions, number of shock waves, fluoroscopy time, wave energy, applied focal energy coefficient, efficiency coefficient, lithiasic fragmentation, lithiasic clearance, residual lithiasis, presence of lithiasis and complications. The results were analyzed with SPSS 17.0 considering statistical significance p≤0.05., Results: Of the 377 patients, 213 were men and 164 women, with a mean age of 51.28 ± 12.77 years. The mean size of the stones in maximum diameter was 11.77 ± 6.13 mm. Lithiasis fragmentation occurred in 81.9% of cases, with a percentage of residual lithiasis after the first session of 58.7% and a total or partial expulsion rate of lithiasis fragments of 68.3%, with global success at the end of sessions of lithotripsy of 69.8%. The overall Efficiency Ratio was 0.42, higher in upper calyx 0.51 and lower in medium calyx 0.35, with significant differences (p<0.05). The only differences were found in relation to the success of lithotripsy treatment (75% versus 64.6%, p=0.02), according to lithiasis size (≤10 mm maximum diameter in comparison to >10 mm). In patients with a DJ catheter there is a higher percentage of residual lithiasis (p=0.006)., Conclusions: Treatment with extracorporeal lithotripsy in small lithiasis and in well-selected patients obtains good results with a low rate of complications regardless of sex and body mass index. more...

Purpose: To determine whether androgen blockade produces metabolic changes in urine and increases the risk of calculi after 1 year of treatment., Materials and Methods: The study included 38 patients, from the period April 2015 to June 2016, diagnosed with locally advanced prostate cancer or lymph node metastasis, and with an indication of androgen blockade. Androgen blockade was started with luteinising hormone-releasing hormone (LHRH) analogues, and a blood specimen, a fasting urine and 24-h urine were collected at the time of inclusion, and then at 1 year of follow-up. A study was performed at baseline and at 1 year with imaging tests. An analysis of the variables was performed with a p ≤ 0.05 considered as statistically significant., Results: The mean age of the patients included in the study was 72.26 ± 6.75 years. As regards the biochemistry parameters, an increase in osteocalcin (from 16.28 ± 9.48 to 25.56 ± 12.09 ng/ml; p = 0.001) and an increase in β-crosslaps (from 0.419 ± 0.177 to 0.743 ± 0.268 ng/ml; p = 0.0001) were observed. In the urinary parameters, a significant increase was observed in the fasting calcium/creatinine ratio (from 0.08 ± 0.06 to 0.13 ± 0.06; p = 0.002) and in the 24-h calcium renal excretion (from 117.69 ± 66.92 to 169.42 ± 107.18 mg; p = 0.0001). Calculi formation was observed in 12 of the 38 patients included (31.6%), with a mean size of 3.33 ± 1.31 mm., Conclusion: Treatment with LHRH analogues, as well as increasing the appearance of metabolic syndrome and speeding up the loss bone mineral density, causes an increase in fasting urine calcium. more...

Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis ( Mtb ) infection, and several polymorphisms located in its gene are associated with risk of tuberculosis in diverse populations. Nevertheless, the genetic resistance/susceptibility to tuberculosis in Argentina is unknown. The IFNG rs1861494 polymorphism (G→A) was reported to alter the binding of transcription factors to this region, influencing IFNG production. Using a case-control study, we found an association between the AA and AG genotypes and tuberculosis resistance (AA vs. GG: odds ratio (OR) = 0.235, p -value = 0.012; AG vs. GG: OR = 0.303, p -value = 0.044; AA vs. AG: OR = 0.776, p -value = 0.427; AA + AG vs. GG: OR = 0.270, p -value = 0.022). Moreover, Mtb -antigen stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors and AA carriers secreted the highest amounts of IFNG in culture supernatants ( p -value = 0.034) and presented the greatest percentage of CD4⁺IFNG⁺ lymphocytes ( p -value = 0.035), in comparison with GG carriers. No association between the polymorphism and clinical parameters of tuberculosis severity was detected. However, our findings indicate that the rs1861494 single nucleotide polymorphism (SNP) could be considered as a biomarker of tuberculosis resistance in the Argentinean population., Competing Interests: The authors declare no conflict of interest. more...

During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen. more...

In this review, we analyze the etiopathogenic principles of urinary lithiasis formation. In the kidney, calcifications that may cause renal lithiasis are produced as a consequence of processes that injury the urothelium at the papilla and Bellini's ducts. With the improvement of imaging techniques, mainly micro CT scan, it is possible to detect them and we may be able to anticipate to the formation of lithiasis. As we well know, there are different factors that influence the formation of the calculi depending on their composition. In calcium lithiasis it is key to review the modification of the categories of hypercalciuria, we currently distinguish two types instead of three, thanks to the fasting calcium/ creatinine ratio, differentiating absorptive hypercalciuria and fasting hypercalciuria. In the fasting hypercalciuria, it is important to emphasize the relationship between this factor and the loss of bone mineral density in patients with recurrent renal calcic lithiasis, so that in this kind of patients it is compulsory the study of bone metabolism by bone remodelling markers and bone densitometry. Regarding the other factors that participate in the formation of calcium lithiasis we should specially emphasize on hypercalciuria and its growing increase because of its relationship with obesity and metabolic syndrome, as well as hipocitraturia, present in an important percentage of patients and related in some cases with metabolic acidosis and osteopenia-osteoporosis too. In relation to uric acid lithiasis it should be highlighted that urinary pH is the most determinant factor and, therefore, its control and modifications would be paramount for prevention of this type of lithiasis. In the infectious lithiasis, the presence of germs that split urea is mandatory. They generate ammonia ions with the ability to injure the urothelium and to form magnesium ammonium phosphate lithiasis mainly. Regarding cystine lithiasis, rare, it was classically divided in three types and now passed to be classified in type A and B depending on the muted gene, and it is more useful to perform direct 24-hour urine measurement than screening tests which have low sensitivity. In general, we tried to give a comprehensive view of the various types of lithiasis emphasizing the most interesting clinical points for the urologist. more...

A 17-year-old adolescent boy was referred to the urology department of our institution for hematospermia after initiation of sexual relationship. A magnetic resonance imaging scan showed giant dilation of a multicystic left seminal vesicle with left renal agenesis. These findings are typical of the Zinner syndrome. In 70%-80% of the cases when renal agenesis is found, there is an ipsilateral cystic dilation of the seminal vesicle that in some cases may be associated with testicular ectopia or absence of the bladder trigone. The ejaculatory ducts, which are formed from the mesonephric system, are abnormally developed in these cases., (Copyright © 2016 Elsevier Inc. All rights reserved.) more...

Dissipation curves of azoxystrobin and of the neonicotinoids acetamiprid and thiacloprid in peach; azinphos-methyl and carbaryl in pear and azoxystrobin, chlorfenapyr and chlorpyrifos in high-tunnel tomato crops were studied in the Southern region of Uruguay. An analytical methodology based on solid phase extraction (SPE) and detection by High Performance Liquid Chromatography with Diode Array Detector (HPLC/DAD) was used for acetamiprid and thiacloprid. Coupled SPE and detection by Gas Chromatography with Mass Selective Detector (GC/MSD) was used for the detection of azinphos-methyl, azoxystrobin, carbaryl, chlorfenapyr and chlorpyrifos residues. Curves were modeled mathematically with Solver program of Microsoft Excel. The best fit for acetamiprid and thiacloprid in peach was achieved with the exponential model (r(2)=0.961 and 0.944, respectively). In the case of peach fruits there is not a Maximum Residue Limit (MRL) for acetamiprid in the Codex Alimentarius, while 0.5 mg/kg is the value rated for thiacloprid. The MRLs accepted by the European Union (EU) are 0.1 mg/kg for acetamiprid and 0.3 mg/kg for thiacloprid. According to the curves determined in these experiments, thiacloprid residues 10 to 12 days after application (daa) were below the MRLs established by both sources. In the case of acetamiprid, 25 daa would be required, according to the exponential mathematical model, to get residues levels below the MRL values established by the EU. For azinphos methyl in pear, the residues detected were mathematically fitted to an exponential model (r(2)=0.999). According to it, residue levels under the MRL established by the EU (0.05 mg/kg) are gotten in our conditions in 20 daa. In plastic tunnel tomato chlorfenapyr residues were not detected from 16 daa, having the dissipation curve an exponential trend. In the same condition, there was not a decay of the azoxystrobin concentration during a 24-day trial, being it around 0.40 ± 0.05 mg/kg. more...