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BACKGROUND: The lack of effectiveness of acute myeloid leukemia (AML) treatment remains a major challenge and resembles a principal cause of AML-related mortality owing to chemotherapy resistance. SNAI1 has been proved to be a leading factor in drug resistance in many cancer types. However, its relation to chemoresistance in AML is not well understood. METHODS: In addition to standard lab work, the expression level of SNAI1 was determined in bone marrow samples of 109 adult and pediatric patients with de novo acute myeloid leukemia using RT-qPCR. The relation between SNAI1 and AML drug resistance and immunomodulatory genes was investigated using the STRING tool. RESULTS: The SNAI1 expression level was upregulated in AML patients in particular samples with promyelocytic leukemia subtype against control cases. In the treatment response, SNAI1 was significantly higher in resistant patients in comparison with the complete remission group. SNAI1 overexpression was associated with high initial blasts and total leukocyte counts, but with HLA class II histocompatibility antigen DR downregulation. STRING analysis showed that multiple drug resistance and immunomodulatory genes of AML induce SNAI upregulation and activation. Kaplan-Meier analysis indicated that there was no relation between SNAI1 expression level and patient survival status. CONCLUSION: We conclude that the SNAI1 expression level may be a predictor of intrinsic drug resistance incidence in AML patients.
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Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Adulto , Humanos , Niño , Médula Ósea , Enfermedad Aguda , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/tratamiento farmacológico , Antígenos HLA-DR/análisis , Antígenos HLA-DR/uso terapéutico , Resistencia a Medicamentos , Factores de Transcripción de la Familia SnailRESUMEN
OBJECTIVE: Hepatitis B is sexually transmitted among men who have sex with men (MSM) and has previously been endemic in some populations of MSM. Presence of anti-hepatitis B core (anti-HBc) determines previous or ongoing infection. We aimed to establish the prevalence and associations of anti-HBc in our clinic population of MSM. METHOD: A cross-sectional study of newly attending MSM to determine the prevalence and associations of testing positive for anti-HBc using our clinic database from 2012 to 2019. We used crude odds ratios to identify any associations. RESULTS: There were 3342/5842 (58%) newly attending MSM who were tested for anti-HBc between 2012 and 2019. Of the 3342 MSM tested for anti-HBc, the median age was 30years (interquartile range 23-43), 442 (13%) were living with HIV, 10 (0.3%) were HBsAg positive, 62 (1.9%) had past/current hepatitis C, 401 (12%) had a positive syphilis enzyme immunoassay (EIA), 455 (14%) were diagnosed with either gonorrhoea or chlamydia and 1080 (32%) were non-UK born. A total of 331 (10%, 95% confidence interval (CI)=8.9-11.0) tested positive for anti-HBc and the proportion testing positive reduced significantly throughout the study period (P <0.004). Testing positive for anti-HBc was associated with age >30years (OR=8.2, 95% CI=5.9-11.4, P <0.0001), having past/current hepatitis C (odds ratio (OR)=5.0, 95% CI=3.0-8.6, P <0.0001), having a positive syphilis EIA (OR=5.9, 95% CI=4.4-7.3, P <0.0001) and being non-UK born (OR=1.4, 95% CI=1.1-1.8, P <0.006). There were no associations with HIV status or having a diagnosis of gonorrhoea or chlamydia. CONCLUSION: Although reducing, the prevalence of anti-HBc remains endemic in MSM locally and further efforts are needed to enhance hepatitis B prevention strategies.
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Chlamydia , Gonorrea , Infecciones por VIH , Hepatitis B , Hepatitis C , Salud Sexual , Minorías Sexuales y de Género , Sífilis , Masculino , Humanos , Adulto , Homosexualidad Masculina , Sífilis/epidemiología , Gonorrea/epidemiología , Prevalencia , Estudios Transversales , Hepatitis B/epidemiología , Infecciones por VIH/epidemiologíaRESUMEN
BACKGROUND: Axillary nerve injury is the most common nerve injury affecting shoulder function. Nerve repair, grafting, and/or end-to-end nerve transfers are used to reconstruct complete neurotmetic axillary nerve injuries. While many incomplete axillary nerve injuries self-resolve, axonotmetic injuries are unpredictable, and incomplete recovery occurs. Similarly, recovery may be further inhibited by superimposed compression neuropathy at the quadrangular space. The current framework for managing incomplete axillary injuries typically does not include surgery. METHODS: This study is a retrospective analysis of 23 consecutive patients with incomplete axillary nerve palsy who underwent quadrangular space decompression with additional selective medial triceps to axillary end-to-side nerve transfers in 7 patients between 2015 and 2019. Primary outcome variables included the proportion of patients with shoulder abduction M3 or greater as measured on the Medical Research Council (MRC) scale, and shoulder pain measured on a Visual Analogue Scale (VAS). Secondary outcome variables included pre- and postoperative Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) scores. RESULTS: A total of 23 patients met the inclusion criteria and underwent nerve surgery a mean 10.7 months after injury. Nineteen (83%) patients achieved MRC grade 3 shoulder abduction or greater after intervention, compared with only 4 (17%) patients preoperatively (p = 0.001). There was a significant decrease in VAS shoulder pain scores of 4.2 ± 2.5 preoperatively to 1.9 ± 2.4 postoperatively (p < 0.001). The DASH scores also decreased significantly from 48.8 ± 19.0 preoperatively to 30.7 ± 20.4 postoperatively (p < 0.001). Total follow-up was 17.3 ± 4.3 months. CONCLUSION: A surgical framework is presented for the appropriate diagnosis and surgical management of incomplete axillary nerve injury. Quadrangular space decompression with or without selective medial triceps to axillary end-to-side nerve transfers is associated with improvement in shoulder abduction strength, pain, and DASH scores in patients with incomplete axillary nerve palsy.
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Plexo Braquial , Transferencia de Nervios , Traumatismos de los Nervios Periféricos , Lesiones del Hombro , Humanos , Estudios Retrospectivos , Dolor de Hombro/cirugía , Resultado del Tratamiento , Plexo Braquial/lesiones , Lesiones del Hombro/cirugía , Traumatismos de los Nervios Periféricos/cirugía , Parálisis/cirugíaRESUMEN
Epigenetics factors are critical for normal cell function and their regulation is sensitive to malignancy development. EHMT2/G9a and KDM2b are key epigenetics players in different cancer types. However, their expression profiles and related consequences in acute myeloid leukemia (AML) patients have not been known yet. In addition to routine lab work, expression levels of EHMT2/G9a and KDM2b were determined in 110 adult and pediatric patients with De Novo AML. Relations between their expression and patients' clinical data were tested by statistical methods. EHMT2/G9a and KDM2b were highly expressed in AML patients against control cases and associated with the presence of adverse genomic alterations. In response to induction chemotherapy, EHMT2/G9a and KDM2b showed to be significantly high in resistant and relapsed patients in comparison to the complete remission group. KDM2b overexpression was associated with CD11c (integrin alpha X) downregulation. Kaplan-Meier analysis indicated that EHMT2/G9a and KDM2b overexpression was correlated with poor survival status in AML patients. We conclude that EHMT2/G9a and KDM2b expression levels could be used as independent prognostic factors for AML disease.
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Cromatina , Leucemia Mieloide Aguda , Adulto , Niño , Epigénesis Genética , Antígenos de Histocompatibilidad/genética , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , PronósticoRESUMEN
Hepatitis A is a sexually transmitted enteric infection in men who have sex with men (MSM). HIV pre-exposure prophylaxis (PrEP) has increased opportunities for sexual health interventions in MSM. 588 (372 in 2019, 216 in 2021) MSM attended for the first time in the study periods. MSM were significantly more likely to be screened for Hepatitis A susceptibility in 2021 than 2019 (93% vs 56%, P =0.0001). Susceptibility (Hepatitis A IgG negative) to Hepatitis A did not change between in 2021 and 2019 (48% vs 47%, P =0.921). De-medicalising PrEP is important as it will increase overall uptake. However, coupling PrEP with other sexual health interventions must not be lost.
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Fármacos Anti-VIH , Infecciones por VIH , Hepatitis A , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Hepatitis A/prevención & control , Homosexualidad Masculina , Humanos , MasculinoRESUMEN
GOALS: Assess outcomes in patients with an index presentation of spontaneous bacterial peritonitis (SBP) over a 13-year period. BACKGROUND: SBP, a bacterial infection of ascites, has a poor prognosis. STUDY: Retrospective cohort study assessing mortality (standardised to 32 months) and prognostic factors in patients with SBP during two periods: period 1 (June 2006-November 2012) and period 2 (December 2012-May 2019). RESULTS: The study included 178 patients who were followed up for 11.6 (29.2) months. Mortality was high, with 12-, 24- and 32-month survival being 32%, 26% and 24%, respectively. Inpatient mortality was 36% with mortality in those surviving hospitalisation being 62%. Serum creatinine at the time of SBP diagnosis was an independent predictor of mortality at 32 months [hazard ratio (HR) 1.002, P = 0.023] and inpatient mortality (HR 1.003, P = 0.035). Positive ascitic fluid culture and ascitic fluid neutrophil count were independent predictors of 32-month (HR 1.679, P = 0.008) and inpatient mortality (HR 1.0001, P = 0.005), respectively. Patients in period 2 had lower ascitic fluid albumin (5.9 ± 3.3 g/L vs. 10.8 ± 5.4 g/L, P < 0.001), higher ascitic fluid neutrophil count (815.0 cells/mm3 vs. 345.0 cells/mm3, P < 0.001) and higher rates of hepatorenal syndrome-acute kidney injury (58 vs. 35%, P = 0.002). Mortality at 32 months and mortality in those surviving hospitalisation were similar at 78 vs. 73%, P = 0.392 and 66 vs. 58%, P = 0.355, for periods 1 and 2, respectively. CONCLUSIONS: Despite more advanced initial presentations, mortality rates have remained similar over the last 13 years. Serum creatinine at the time of SBP diagnosis is an independent predictor of mortality.
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Infecciones Bacterianas , Peritonitis , Humanos , Cirrosis Hepática/diagnóstico , Estudios Retrospectivos , Creatinina , Líquido Ascítico/microbiología , Ascitis , Infecciones Bacterianas/diagnóstico , Peritonitis/microbiología , HospitalizaciónRESUMEN
This study was aimed to examine the clinical utility and impact of the 2016 Banff criteria for acute antibody-mediated rejection (acute AMR) in patients with liver transplantation. Among adult patients with donor-specific antibody (DSA) assays performed between 2015 and 2020, cases with proved DSA (mean fluorescent index >2000) and matched liver biopsy available were reviewed. Among 55 patients identified, 28 (51%) had class I DSA, 45 (82%) had class II DSA and 18 (33%) had both. Mild, moderate and severe microvasculitis were observed in 11 (20%), 2 (4%) and 1 (2%) case, respectively. Diffuse immunoreactivity to C4d on portal microvascular endothelia was confirmed in 5 cases (9%), which met the criteria of definite (n = 2) or suspicious for acute AMR (n = 3). Cases of acute AMR more commonly had class I DSA (100% vs. 46%; p = 0.027) or both class I and II DSA (80% vs. 28%; p = 0.018) than cases of non-acute AMR. One case of pure acute AMR with veno-occlusion was successfully treated with plasma exchange. The remaining 4 cases had features of combined acute AMR/T cell-mediated rejection (TCMR), and two progressed to ductopenic rejection within 3 weeks. In conclusion, only 9% of DSA-positive patients met the Banff criteria for acute AMR, necessitating careful morphological and immunohistochemical assessments of the allograft biopsies according to the proposed standards. Combined acute AMR/TCMR was more common than isolated acute AMR, and additional AMR in TCMR cases may be associated with rapid progression to ductopenic rejection.
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Trasplante de Riñón , Trasplante de Hígado , Adulto , Aloinjertos , Anticuerpos , Biopsia , Complemento C4b , Rechazo de Injerto , Humanos , Hígado , Fragmentos de PéptidosRESUMEN
BACKGROUND: Genomic abnormalities were established as prognostic and diagnostic markers for acute myeloid leukemia (AML) tumorgenesis and YBX1 gene has important roles in different cancer types. METHODS: A total of 109 adult and pediatric patients with De novo AML, were enrolled in this study. Besides the routine lab work; bone marrow YBX1 expression levels were measured using qRT-PCR, and then its possible connections to AML pathogenesis pathway were investigated by STRING tool. RESULTS: Results demonstrated upregulation of YBX1 expression level in AML patients that was associated with the presence of adverse genomics abnormalities. In adult patients, the level of YBX1 expression was significantly high in relapsed and resistant groups, while in pediatric patients, the level of YBX1 expression showed an inverse pattern as it was highly expressed in complete remission group. STRING analysis highlighted that YBX1 interacts with important factors in the AML signaling pathway. Kaplan-Meier analysis indicated that adult patients with highly expressed YBX1 significantly endured shorter disease-free survival (DFS) compared to low YBX1 expressers and there was no impact of YBX1 on adult patients overall survival (OS). While pediatric patients with upregulated YBX1 showed good OS over downregulated patients. CONCLUSION: In conclusion, YBX1 may have a crucial role in AML relapse pathogenesis. Also, it could serve as a prognostic factor for AML disease outcomes.
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Leucemia Mieloide Aguda , Adulto , Niño , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Pronóstico , Recurrencia , Proteína 1 de Unión a la Caja Y/genéticaRESUMEN
Caustic injury secondary to impaction of ingested batteries is a potentially severe cause of oesophageal injury with an increasing incidence that reflects consumer trends and the utilisation of compact electronic devices. Delays to recognition and management are associated with increased risk of complications, morbidity and mortality. In this manuscript, we describe a case presentation and literature review of a patient presenting with upper oesophageal odynophagia after the deliberate ingestion of multiple foreign bodies.
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Quemaduras Químicas , Trastornos de Deglución , Enfermedades del Esófago , Cuerpos Extraños , Golondrinas , Adolescente , Animales , Quemaduras Químicas/etiología , Trastornos de Deglución/complicaciones , Femenino , Cuerpos Extraños/complicaciones , HumanosRESUMEN
Background: The impact of continuous positive airway pressure (CPAP) on cardiovascular outcomes among patients with obstructive sleep apnea (OSA) is controversial. Objective: To evaluate the impact of CPAP on reducing cardiovascular outcomes in patients with OSA. Methods: We performed a computerized search of MEDLINE, EMBASE and COCHRANE databases through April 2021 for randomized trials evaluating the impact of CPAP versus control on cardiovascular outcomes in patients with OSA. Summary estimates were reported using both fixed and random effects model. The main study outcome was major adverse cardiac events (MACE). Results: The final analysis included 8 randomized trials with total of 5684 patients. The weighted mean follow-up was 42.6 months. There was no difference between the CPAP and control groups in the risk of MACE (14.4% versus 14.8%, risk ratio [RR]: 0.97; 95% confidence interval [CI]: 0.85 to 1.10; p = 0.60; I2 = 21%). Subgroup analysis suggested that CPAP was associated with lower MACE (by 36%) in CPAP-adherent patients (≥4 h/night) (Pinteraction = 0.08). There was no difference between the CPAP and control groups in the risk of all-cause mortality, cardiovascular mortality, acute stroke, acute myocardium infarction or hospitalizations for angina. Conclusions and relevance: CPAP use might not be associated with lower cardiovascular events among patients with OSA. However, patients adherent to CPAP (≥4 h/night) might derive a benefit on cardiovascular outcomes. Future studies are warranted to evaluate the impact of CPAP in reducing cardiovascular events among patients with severe OSA and with optimal adherence rates to CPAP therapy.
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This work aimed to study the solvation properties of newly synthesized cationic surfactants: 1-hexyl-1-methyl-1H-imidazol-1-ium bromide (R6Im), 1-dodecyl-1-methyl-1H-imidazol-1-ium bromide (R12Im), N,N,N-tributylhexan-1-aminium bromide (R6N4), and N,N,N-tributyldodecan-1-aminium bromide (R12N4) in water and ethanol-water solvents with a 0.237 mole fraction of ethanol at 298.15 K using conductivity, refractive index, surface tension, and density measurements. Critical micelle concentration (CMC) for the synthesized surfactants was determined and discussed. Thermodynamic parameters including association constant, molal volume, and polarizability were calculated and discussed. Some surface properties of surfactants including excess surface concentration and minimum area per molecule were also calculated and discussed. A good agreement was found between the CMC values obtained from different techniques, such as conductivity, refractive index, and surface tension. Imidazolium surfactants had been proved to decrease the CMC and increase the association constant with the increase of ethanol mole fraction, while tributylamine had been proved to increase the CMC and decrease the association constant with the increase of ethanol mole fraction. Also, imidazolium surfactants had been proved to have higher CMC than tributylamine, which may be related to higher solvation of imidazolium surfactants than that of tributylamine. Both surfactants (R12Im) and (R12N4) were proved to have lesser CMC.