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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks an actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure is often encountered due to inherent or acquired resistance to chemotherapy. Previous studies implicated PI3K/Akt/mTOR signaling pathway in cancer stem cells (CSCs) enrichment and hence chemoresistance. The present study aimed at investigating the potential effect of piperine (PIP), an amide alkaloid isolated from Piper nigrum, on enhancing the sensitivity of TNBC cells to doxorubicin (DOX) in vitro on MDA-MB-231 cell line and in vivo in an animal model of Ehrlich ascites carcinoma solid tumor. Results showed a synergistic interaction between DOX and PIP on MDA-MB-231 cells. In addition, the combination elicited enhanced suppression of PI3K/Akt/mTOR signaling that paralleled an upregulation in this pathway's negative regulator, PTEN, along with a curtailment in the levels of the CSCs surrogate marker, aldehyde dehydrogenase-1 (ALDH-1). Meanwhile, in vivo investigations demonstrated the potential of the combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities. Notably, the combination failed to change cleaved poly-ADP ribose polymerase levels suggesting a pro-necrotic rather than pro-apoptotic mechanism. Overall, these findings suggest a potential role of PIP in decreasing the resistance to DOX in vitro and in vivo, likely by interfering with the PI3K/Akt/mTOR pathway and CSCs.
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Alcaloides , Benzodioxóis , Doxorrubicina , Células-Tronco Neoplásicas , Fosfatidilinositol 3-Quinases , Piperidinas , Alcamidas Poli-Insaturadas , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Neoplasias de Mama Triplo Negativas , Doxorrubicina/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Piperidinas/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Humanos , Alcaloides/farmacologia , Benzodioxóis/farmacologia , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Sinergismo Farmacológico , Camundongos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
Background and objectives: The elderly population is affected by chronic diseases and lifelong medication. The American Geriatrics Society (AGS) Beers Criteria is a comprehensive approach to medication usage in the older population to reduce potentially inappropriate medication (PIM) use. The purpose of this study was to assess the usage of PIMs in elderly patients upon discharge from tertiary care hospital settings in Riyadh, Saudi Arabia, using the AGS Beers Criteria 2019. Methods: The data was obtained from the medical records of 1237 patients (>65 years) who were discharged from medical or surgical wards at two hospitals affiliated with King Abdulaziz Medical City. The data was analyzed to determine the prevalence of PIM prescription, and the proportional odds of the independent factors influencing outcomes were estimated using ordinal regression analysis for criteria 1 and 2, while Binary regression analysis was conducted for criterion 3. Results: There were approximately equal numbers of male and female participants in our study (male: 50.8 % vs. female: 49.2 %). One-third of the patients were above the age of 80 years, with 41 % being between the ages of 70 and 80 years. Moreover, almost 70 % of the samples had chronic illnesses. The overall prevalence of PIMs was 29.2 %, with 11 % of PIMs to be avoided in elderly patients and 17 % to be used with caution in the elderly, while disease-specific PIMs were identified in 1.2 % of the patients. The most common PIM class was proton pump inhibitors (44.41 %), and patients discharged from the surgical unit were more likely to be prescribed PIMs. Proton pump inhibitors (44.41 %) were the most inappropriately prescribed drug class, and patients discharged from the surgical unit were more likely to be prescribed PIMs. Conclusion: The study noticed that male gender, the presence of multiple diseases, and obesity are associated with more than one PIM prescription. There is a need to streamline the surgical department's prescription procedure to eliminate prescription disparities. Prescription monitoring is recommended to avoid medication errors, particularly in patients who are taking multiple medications.
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BACKGROUND AND OBJECTIVE: Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). RESULTS: We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). CONCLUSION: PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.
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Vacinas Antimaláricas , Malária Falciparum , Plasmodium falciparum , Ensaios Clínicos Controlados Aleatórios como Assunto , Esporozoítos , Vacinas Atenuadas , Humanos , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/uso terapêutico , Malária Falciparum/prevenção & controle , Malária Falciparum/imunologia , Parasitemia/prevenção & controle , Plasmodium falciparum/imunologia , Esporozoítos/imunologia , Vacinas Atenuadas/imunologiaRESUMO
Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.
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Curcumina , Piretrinas , Humanos , Ratos , Animais , Curcumina/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo , Piretrinas/toxicidade , Apoptose , Corantes , PulmãoRESUMO
The clinical outcome of lymphocytic leukemia (CLL) is quite heterogeneous. The purpose of this observational study was to investigate the clinical merit of measuring plasma galectin-9 and CXCL-13 concentrations as predictors of CLL activity, prognosis, and early indicators of therapeutic response. These biomarkers were compared with other prognostic indicators, progression-free survival (PFS), time to first treatment (TTT), and overall survival (OS) over a follow-up period (4 years). First, plasma galectin-9 and CXCL-13 concentrations were analyzed in CLL patients at the time of diagnosis as well as healthy controls. Compared to controls, CLL patients had significantly higher serum levels of CXCL-13 and galectin-9. Second, we observed that CLL patients with high soluble CXCL-13 and galectin-9 levels had advanced clinical stages, poor prognosis, 17p del, short PFS, short TTT, and therapy resistance. The levels of CXCL-13, ß2-microglobulin, LDH, CD38%, and high grade of Rai-stage were all strongly correlated with the galectin-9 levels. Soluble CXCL-13 and galectin-9 had very good specificity and sensitivity in detecting CLL disease progression and high-risk patients with the superiority of galectin-9 over CXCL-13. Although the two biomarkers were equal in prediction of TTT and treatment response, the soluble CXCL13 was superior in prediction of OS. High CXCL-13 and galectin-9 plasma levels upon CLL diagnosis are associated with disease activity, progression, advanced clinical stages, short periods of PFS, short TTT, and unfavorable treatment response.
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Leucemia Linfocítica Crônica de Células B , Humanos , Biomarcadores , Quimiocinas CXC , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/terapia , Ligantes , Prognóstico , Intervalo Livre de ProgressãoRESUMO
Robotic-assisted surgery is a computer-controlled technique that may improve the accuracy and outcomes of unicompartmental total knee arthroplasty (TKA), a partial knee replacement surgery. The purpose of a meta-analysis about robotic-assisted versus conventional surgery for unicompartmental TKA is to compare the effectiveness of these two methods based on the current evidence. Our meta-analysis can help inform clinical decisions and guidelines for surgeons and patients who are considering unicompartmental TKA as a treatment option. We searched four online databases for studies that compared the two methods until March 2023. We used RevMan software to combine the data from the studies. We calculated the mean difference (MD) and the 95% confidence interval (CI) for each outcome, which are statistical measures of the difference and the uncertainty between the two methods. We included 16 studies in our analysis. We found that robotic-assisted surgery had a better hip-knee-ankle angle, which is a measure of how well the knee is aligned, than conventional surgery (MD = 0.86, 95% CI = 0.16-1.56). We also found that robotic-assisted surgery had a better Oxford Knee score, which is a measure of how well the knee functions, than conventional surgery (MD = 3.03, 95% CI = 0.96-5.110). This study compared the results of conventional and robotic-assisted unicompartmental knee arthroplasty in 12 studies. We concluded that robotic-assisted surgery may have some benefits over conventional surgery in terms of alignment and function of the knee. However, we did not find any significant difference between the two methods in terms of other outcomes, such as pain, range of motion, health status, and joint awareness. Therefore, we suggest that more research is needed to confirm these results and evaluate the long-term effects and cost-effectiveness of robotic-assisted surgery.
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BACKGROUND: Taxane-induced peripheral neuropathy (TIPN) among breast cancer patients is considered one of the most devastating side effects affecting compliance to chemotherapy protocol and patients' quality of life (QOL). OBJECTIVES: This trial aimed to evaluate the effect of lidocaine infusion vs oral duloxetine on the incidence and severity of TIPN and QOL in patients with breast cancer scheduled for neoadjuvant taxane therapy (TT). STUDY DESIGN: Prospective, randomized, single-blinded, controlled trial. SETTING: This study was carried out on 60 patients with breast cancer scheduled for 12 weeks of TT at the Medical Research Institute Hospital, Alexandria University after obtaining local Ethics Committee approval (IORG008812) and getting a written informed consent from each patient. It was registered in the "clinical trials library for protocol registration and results system" with the number NCT04732455. METHODS: Sixty women scheduled for TT weekly for 12 weeks, were randomly allocated to receive intravenous saline infusion in the control group (GC), or lidocaine 2mg/kg with saline infusion in the lidocaine group (GL), or saline infusion and 30 mg duloxetine in the duloxetine group (GD). All infusions were administered over 40 minutes before each TT. Oral duloxetine was prescribed once daily starting from the night before commencing TT and continued for 12 weeks. Douleur Neuropathique en 4 Questions (DN4) questionnaire was filled weekly to detect the incidence of neuropathic pain (NP). The nerve conduction study (NCS) aimed to detect and measure the degree of neuropathy before starting the chemotherapy protocol and post-12 weeks of Taxol Therapy. NP Scale was measured weekly to assess the severity of NP symptoms. Patients' QOL was evaluated by the European Organization for Research and Treatment of Cancer QOL Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale. RESULTS: Thirty-five percent of patients reported DN4 > 4 points in GC after 6 weeks of TT in comparison to 5% in GL and 0% in GD (P = .005). Moreover, the incidence rose to 75% in GC compared to 20% in GL and 25% GD at the end of TT (P < 0.001). The severity of symptoms, global pain intensity, and patients' unpleasantness were significantly more in GC than GL and GD in the last 4 weeks of TT (P < 0.05). NCS showed that 55% and 25% of patients developed mild and moderate axonal neuropathy, respectively, in GC. In contrast, mild neuropathy was developed in 20% and 25% of patients in GL and GD, respectively, and moderate neuropathy in 5% in both groups. The negative impact of TT on QOL was more significant in GC than GL and GD at weeks 8 and 12 of TT (P < 0.001). LIMITATIONS: Limited reference data for all treatment regimens to include in the Discussion section. CONCLUSIONS: Lidocaine and duloxetine have a comparable effect to decrease the incidence and severity of TIPN. Moreover, patients' QOL was significantly better in both groups. KEY WORDS: Lidocaine infusion, duloxetine, taxane-induced peripheral neuropathy, breast cancer, DN4.
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In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.
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Hipopigmentação , Terapia Ultravioleta , Vitiligo , Humanos , Dinoprostona , Dinoprosta , Vitiligo/radioterapia , ProstaglandinasRESUMO
INTRODUCTION: Hyperhidrosis is excessive sweating beyond thermoregulatory needs. It is a potentially disabling condition with challenging management. Aluminum chloride is the established topical treatment; however, response remains unsatisfactory. Oxybutynin is an anticholinergic drug that stands as a therapeutic chance for hyperhidrosis. OBJECTIVES: comparing the efficacy of topical oxybutynin 3% gel versus aluminum chloride 15% lotion in treatment of primary focal hyperhidrosis. METHODS: Forty patients with hyperhidrosis were randomly distributed into 2 equal groups treated by either topical oxybutynin 3% gel or topical aluminum chloride 15% lotion once daily night application for 4 weeks (both groups). Evaluation was done at 2 and 4 weeks of treatment and after 1 month of the end of treatment for follow up by Minor iodine starch test, hyperhidrosis disease severity scale (HDSS) and dermatology life quality index (DLQI). RESULTS: Both treatment modalities were effective with insignificant differences between patients of both groups regarding improvement in Minor iodine starch test and HDSS after 2 weeks of treatment (P = 0.561, 0.33 respectively). Oxybutynin 3% gel yielded significantly better improvement of Minor's test, HDSS and patient's quality of life at the end of 4 weeks of treatment with lower recurrence rate than aluminum chloride 15% lotion at 1 month follow up. Minimal adverse effects were noted in both studied groups. CONCLUSIONS: Oxybutynin 3% gel could be considered as a promising treatment modality for hyperhidrosis with higher efficacy than aluminum chloride 15% lotion and lower recurrence rate.
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BACKGROUND: Atrial fibrillation (AF) is the most common form of dysrhythmia observed in the clinical field, causing multiple morbidities, such as thromboembolic complications. Hence, the maintenance of sinus rhythm is superior to rate control. This study tests the efficacy of single- and low-dose amiodarone on the persistence of AF after surgery before transfer to the intensive care unit. METHODS: A double-blinded, randomized controlled trial assessed 113 patients who underwent mitral valve surgery with preoperative chronic AF. Patients were divided into two groups: the control group (N = 55) who received 50 mL of 5% dextrose over 10 min after general anesthesia induction, and the amiodarone group (N = 58) who received 1 mg/kg of amiodarone diluted in 50 mL of 5% dextrose over 10 min shortly after anesthesia induction. RESULTS: The amiodarone group had a statistically significant successful conversion of preoperative AF to normal sinus rhythm in 40 patients (72.73%). The control group demonstrated spontaneous conversion from AF to a normal sinus rhythm in seven patients (12.73%). The sinus rhythm was maintained in 60% of patients (36), as four patients reverted to AF during the hospital stay despite the initial normal sinus rhythm after the operation. In contrast, 53 (96.36%) patients in the control group were discharged from the hospital with a controlled rate of AF. In addition, low-dose amiodarone caused a statistically significant reduction in heart rates at 10, 30, and 60 min after declamping, extended throughout the first 24 h with mean heart rates of 97.233±7.311, 99.509±8.482, and 97.940±7.715 bpm, respectively. In comparison, the control group had heart rates of 115.382±7.547, 115.055±13.919, and 113.618±8.765 bpm at these times. The mean postoperative heart rate at the end of the first 24 h was 97.793±7.189 bpm in the amiodarone group and 113.036±9.737 bpm in the control group. No mortality or need for mechanical support was recorded in either group. CONCLUSIONS: Single and low-dose intraoperative intravenous amiodarone during mitral valve surgery may be practical to aid in pharmacological cardioversion of patients with preoperative chronic AF presenting for mitral valve surgery.
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Amiodarona , Fibrilação Atrial , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Cardioversão Elétrica , Glucose/uso terapêutico , Humanos , Valva Mitral/cirurgia , Resultado do TratamentoRESUMO
Endoscopic retrograde cholangiopancreatography (ERCP) identifies and treats pancreatic and biliary diseases. We conducted a systematic review and meta-analysis examining relevant papers in five databases to examine the frequency of hypoxia throughout the surgery and the lowest oxygen saturation level in patients under sedation. Our meta-analysis included three randomized controlled trials with 390 participants, 196 in the high-flow oxygen (HFNC) group and 194 in the low-flow oxygen (LFNC) group. Their ages ranged from 65.3 to 79 years. The pooled effect estimate showed that HFNC decreased the incidence of hypoxia during the procedure when compared to LFNC (odds ratio -0.84; 95% confidence interval [CI] -1.65, -0.02; P = 0.04), and the mean of lowest oxygen saturation in patients during sedation was significantly lower in LFNC compared to HFNC (mean difference 2.34; 95% CI 1.35, 3.32; P = 0.001). The pooled effect estimate showed that the HFNC group had a lower incidence rate of jaw thrusting adverse events during anesthesia than the LFNC group (risk difference -0.12; 95% CI -0.21, -0.04; P = 0.001). In summary, HFNC systems reduced the incidence of hypoxia for patients undergoing ERCP and had a higher mean lowest oxygen saturation during sedation.
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BACKGROUND AND AIM: Ischemic mitral regurgitation (IMR) is a serious consequence of coronary artery disease. The choice of the optimal surgical strategy remains debatable. The aim of the present meta-analysis is to compare the outcomes of mitral valve repair (RPR) versus replacement (RPL) regarding perioperative mortality, overall mortality, reoperation, recurrence of MR, and reverse remodeling after surgery. METHODS: Electronic searches were performed using the searchable databases of Google Scholar, Pubmed, and Embase, and the search terms mitral valve, IMR, RPR, RPL, and coronary artery bypass grafting. The main outcomes of interest are perioperative mortality, overall mortality, reoperation, recurrence of MR, and reverse remodeling after surgery. Perioperative mortality was defined as death during the surgery or within 30 days after the operation. RESULTS: There was a trend towards better perioperative survival in the RPR arm. However, the difference fell short of statistical significance [odds ratio (OR) (95% confidence interval [CI]): 0.66 (0.41-1.07), p = 0.09]. Patients submitted to RPR experienced a significantly higher MR recurrence rate when compared with their counterparts submitted to RPL [OR (95% CI): 16.8 (5.07-55.7, p = 0.00001)]. CONCLUSION: There is a trend towards lower perioperative mortality in RPR in comparison to RPL. On the other hand, RPL was associated with significantly lower recurrence rates.
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Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral , Isquemia Miocárdica , Humanos , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/complicações , Isquemia Miocárdica/complicações , Isquemia Miocárdica/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer with substantial cancer-related deaths worldwide. Deregulation of some genetic polymorphisms has been identified in HCC. OBJECTIVE: We aimed to demonstrate the frequency of miRNA 196a2 rs11614913 and miRNA 34 b/c rs4938723 gene polymorphisms in HCC patients and their correlation with the clinical features and laboratory findings at diagnosis. SUBJECTS AND METHODS: The study was performed on 40 patients with newly diagnosed HCC and 40 patients with liver cirrhosis in addition to 40 age and sex-matched healthy controls. Detection of miRNA 196a2 rs11614913 and miRNA 34 b/c rs4938723 gene polymorphisms was determined by PCR-RFLP. RESULTS: HCC patients had significantly higher frequency of miR-196-2a rs11614913 CC genotype when compared with cirrhotic patients (60.0 % versus 30.0 %, p=0.013). In spite of the fact that HCC patients also had higher frequency of miR-196-2a rs11614913 CC genotype in comparison to controls, the difference fell short of statistical significance (60.0 % versus 42.5 %, p=0.18). No significant differences were found between the studied groups regarding the frequency of miR-196-2a alleles. miR34 b/c rs4938723 CC genotype was the only identified genotype in all participants in the three studied groups. No significant associations were found between the different clinical and laboratory variables and genotypic variations in HCC patients. CONCLUSIONS: This study identified miR-196a2 rs11614913 CC genotype as a risk factor for HCC development while we failed to document similar relation for miR-34b/c rs4938723 polymorphism.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/genética , Egito/epidemiologia , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The Cardiac Surgery-Associated Neutrophil Gelatinase-Associated Lipocalin (CSA-NGAL) score has been developed to stratify patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Its predictive power needs to be validated to guide clinical decision for such high-risk patients. METHODS: A prospective study was conducted on 637 consecutive adult patients who developed postoperative AKI after cardiac surgery with cardiopulmonary bypass. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria (KDIGO). The CSA-NGAL score was calculated. Assessment of the diagnostic performance of the scoring model was performed by area under the receiver operating curve analysis. RESULTS: The area under the curve for the postoperative Urinary NGAL showed an area under the curve ([standard error (SE)] 0.80 (0.38); p<0.001; 95% CI 0.72-0.87). Its sensitivity for CSA-AKI in the first 24 hours was 66% and specificity was 80% (cut-off value 300.1 ng/mL). There was a positive correlation between NGAL score and KDIGO criteria, with a significant increase in postoperative mean Urinary NGAL values as the KDIGO stage increased. CONCLUSION: The CSA-NGAL score has a high sensitivity, specificity and positive predictive value that can translate into improved outcomes and resource allocation. It is believed that adding it to the existing clinical scoring systems for AKI prediction will be productive.
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Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Proteínas de Fase Aguda , Biomarcadores , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Lipocalina-2 , Lipocalinas , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Proteínas Proto-OncogênicasRESUMO
ABSTRACT BACKGROUND: Hypoxemia and pulmonary complications are common after upper abdominal surgery (UAS). OBJECTIVE: To examine whether inclusion of autogenic drainage (AD) in chest physiotherapy after UAS confers additional benefits in improving blood gases and reducing postoperative pulmonary complications (PPCs). DESIGN AND SETTING: Randomized controlled study conducted at Kasr Al-Ainy teaching hospital, Egypt. METHODS: A randomized controlled trial was conducted on 48 subjects undergoing elective UAS with high risk of developing PPCs. The study group received AD plus routine chest physiotherapy (deep diaphragmatic breathing, localized breathing and splinted coughing) and the control group received routine chest physiotherapy only. The outcomes included arterial blood gases measured at the first and seventh postoperative days, incidence of PPCs within the first seven days and length of hospital stay. RESULTS: Baseline characteristics were similar between groups. In the AD group, SaO2, PaO2, PaCO2 and HCO3 significantly improved (P < 0.05) while in the physiotherapy group, only SaO2 and PaO2 significantly improved (P < 0.05). Nonetheless, significant differences in post-treatment SaO2 and PaO2 between the groups were observed. The overall incidence of PPCs was 16.66% (12.5% in the AD group and 20.8% in the physiotherapy group) (absolute risk reduction -8.3%; 95% confidence interval, CI, -13.5 to 29.6%), with no significant difference between the groups. The AD group had a significantly shorter hospital stay (P = 0.0001). CONCLUSION: Adding AD to routine chest physiotherapy after UAS provided a favorable blood gas outcome and reduced the length of hospital stay. It tended to reduce the incidence of PPCs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04446520.
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Humanos , Modalidades de Fisioterapia , Procedimentos Cirúrgicos Eletivos , Complicações Pós-Operatórias/prevenção & controle , Drenagem , Gases , Tempo de InternaçãoRESUMO
BACKGROUND: Hypoxemia and pulmonary complications are common after upper abdominal surgery (UAS). OBJECTIVE: To examine whether inclusion of autogenic drainage (AD) in chest physiotherapy after UAS confers additional benefits in improving blood gases and reducing postoperative pulmonary complications (PPCs). DESIGN AND SETTING: Randomized controlled study conducted at Kasr Al-Ainy teaching hospital, Egypt. METHODS: A randomized controlled trial was conducted on 48 subjects undergoing elective UAS with high risk of developing PPCs. The study group received AD plus routine chest physiotherapy (deep diaphragmatic breathing, localized breathing and splinted coughing) and the control group received routine chest physiotherapy only. The outcomes included arterial blood gases measured at the first and seventh postoperative days, incidence of PPCs within the first seven days and length of hospital stay. RESULTS: Baseline characteristics were similar between groups. In the AD group, SaO2, PaO2, PaCO2 and HCO3 significantly improved (P < 0.05) while in the physiotherapy group, only SaO2 and PaO2 significantly improved (P < 0.05). Nonetheless, significant differences in post-treatment SaO2 and PaO2 between the groups were observed. The overall incidence of PPCs was 16.66% (12.5% in the AD group and 20.8% in the physiotherapy group) (absolute risk reduction -8.3%; 95% confidence interval, CI, -13.5 to 29.6%), with no significant difference between the groups. The AD group had a significantly shorter hospital stay (P = 0.0001). CONCLUSION: Adding AD to routine chest physiotherapy after UAS provided a favorable blood gas outcome and reduced the length of hospital stay. It tended to reduce the incidence of PPCs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04446520.
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Procedimentos Cirúrgicos Eletivos , Modalidades de Fisioterapia , Drenagem , Gases , Humanos , Tempo de Internação , Complicações Pós-Operatórias/prevenção & controleRESUMO
Introduction: our study aimed to assess the safety and efficacy of Holmium: YAG laser internal urethrotomy compared to the cold knife internal urethrotomy. Methods: Eighty adult male patients presented with a urethral stricture less than 1.5 cm were included in our study; they were randomly allocated into 2 groups representing Holmium and cold knife internal urethrotomy. A careful evaluation with ascending cystourethrogram and uroflowmetry were done on all patients, and they were followed up for 1 year with uroflowmetry. Results: Each group included 40 patients sharing the same demographic data. The most common cause of a urethral stricture in both groups was iatrogenic injury. The mean operative time of the cold knife urethrotomy procedure was 10.98 ± 2.40 minutes compared to 15.43 ± 2.48 minutes in the holmium laser urethrotomy group with a highly significant difference. The results showed success rates of 90% and 80% for the holmium laser and cold knife internal urethrotomy groups respectively. The perioperative complication according to the Clavien-Dindo classification, showed no statistically significant difference in grade 1 and 2 complications. A recurrence rate with the need for redo surgery representing grade 3B complication was seen in 4 cases in the Holmium group compared to 8 cases in the cold knife group with a statistically significant difference. Conclusion: Both Holmium Laser and cold knife internal urethrotomy are an effective surgical option for the treatment of a urethral stricture less than 1.5 cm with a promising outcome after 1-year follow-up with a better success rate using the Holmium laser.
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The present study aimed to assess the impact of retrograde autologous priming (RAP) on hemodynamics and pulmonary mechanics in children subjected to cardiothoracic surgery. This prospective randomized study analyzed the clinical records of 124 children with risk adjustment in congenital heart surgery-1 left to right lesions subjected to cardiac surgery. They comprised 64 patients in RAP group and 60 patients in the conventional priming group. The preoperative, intraoperative and postoperative data of the studied patients were reported. The outcome measures included hematocrit (Hct) value, blood gases, lung mechanics parameters, transfusion needs, ICU stay, postoperative complications and mortality. Preoperatively, there were no significant differences between the studied groups regarding the demographic data, underlying lesions, laboratory data, blood gases and pulmonary mechanics parameters. Intraoperatively, RAP group patients had significantly lower amount of blood loss, less frequent need to packed red blood cells (RBC)s transfusion and better Hct values when compared with the control group. Postoperatively, RAP group patients had significantly higher Hct% at ICU arrival, significantly better pulmonary mechanics parameters and significantly shorter duration on mechanical ventilation. RAP in children older than 12 months subjected to cardiac surgery for risk adjustment in congenital heart surgery-1 left to right lesions is associated with less transfusion needs and better pulmonary mechanics.
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Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Transfusão de Sangue Autóloga/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Criança , Hemodinâmica , Humanos , Lactente , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Estudos Prospectivos , Resultado do TratamentoRESUMO
Inherited thrombocytopenias are a heterogeneous group of diseases characterized by a reduced number of platelets and a bleeding tendency that ranges from very mild to life threatening especially in surgery. Mutations in the 5' untranslated region (UTR) of Ankirin repeat domain 26 (ANKRD26) are responsible for autosomal-dominant form of thrombocytopenia, that is known as ANKRD26-related thrombocytopenia (ANKRD26 RT), characterized by a moderate thrombocytopenia with mild propensity to bleeding and predisposition to hematological malignancies including AML and MDS. We included 90 unrelated patients with inherited thrombocytopenia. In addition, we investigated 45 patients with ITP. Peripheral blood and bone marrow samples were collected and examined and molecular detection of mutations in the 5︡ UTR of ANKRD26 gene was performed for all the patients. Also, screening of the mutation and development of myeloid malignancies in the extended series of the affected subjects was done. ANKRD26 mutations were identified in 10% of the patients with inherited thrombocytopenia. The most common types were c.128 G > A and c.127A>T, while no mutations were found in the ITP group. In those affected, the median number of platelets was 69 x109/L (43-106) with normal MPV in most of the patients (9.4-11.6). There was a statistically significant increase in the unexpected high frequency of myeloid malignancies in the extended series of the mutated subjects compared with the ITP group-extended series (P < .001). So, we can conclude that ANKRD26 RT is associated with increased risk for developing myeloid malignancies and ANKRD26 mutations can represent a valuable tool for making therapeutic decisions.
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Regiões 5' não Traduzidas/genética , Neoplasias Hematológicas/etiologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Trombocitopenia/complicações , Adolescente , Adulto , Idoso , Criança , Egito , Feminino , Predisposição Genética para Doença , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Adulto JovemRESUMO
Background: In the past years, saprophytic bacteria and candida have been emerging as potential human pathogens causing life-threatening infections in patients with cancer. This study was designed to determine the bacteria and candida species, causing bloodstream infections in cancer patients and the assessment of their susceptibility to antibiotics and biosynthesised silver nanoparticles. Materials and Methods: Ninety-seven microbial pathogens recovered from blood samples of cancer patients were included in the present study. The microbial isolates were collected in a duration period extending from December 2016 to July 2018 at National Cancer Institute, Cairo, Egypt. The clinical samples were collected using microbiological methods and were cultivated on MacConkey agar, blood agar media and Sabouraud dextrose agar media. The microbial isolates were identified using both standard microbiological methods and VITEK 2 compact automated system. The antibiotic resistance pattern was determined by the VITEK 2 compact automatic system and disk diffusion method, according to the Clinical and Laboratory Standards Institute. The characterisation of nanoparticles was carried out using ultraviolet spectroscopy and electron microscope. The antimicrobial activity of bio (AgNPs) was evaluated. Results: A total of 97 microbial isolates recovered from collected blood samples from cancer patients were included in the study. Pathogenic bacteria and Candida were represented by 74 isolates (76.22%) and 23 isolates (23.69), respectively. Among the 74 bacterial isolates, Escherichia coli constituted (27.81%), Klebsiella pneumoniae (24.72%), Acinetobacter baummannii (11.33%), Pseudomonas aeruginosa (4.12%), Enterobacter spp. (3.09%) and) Staphylococcus aureus (2.06%). Cedecea davisae (1.03%), Burkholderia cepacia (1.03%) and Pantoea agglomerans (1.03%). Among the 23 Candida isolates, Candida tropicalis constituted (9.27%), Candida albicans (5.15%), Candida glabrata (5.15%) and Candida krusei (4.12%) from the total microbial isolates. The antibiotic susceptibility results revealed that amikacin and gentamycin were the most effective antibiotics against Gram-negative bacteria, while vancomycin and linezolid were most effective against S. aureus. Caspofungin was the most effective against candida species. The obtained stable biosynthesised silver nanoparticles ranged in size from 10 nm to 100 nm and were mostly spherical in shape. These biosilver nanoparticles showed the highest antimicrobial activity against most of the microbial isolates (bacteria and Candida). The in vitro cytotoxicity of biosynthesised AgNPs on HeLa cell lines revealed a dose-dependent potential. The IC50 value of AgNPs was found 6 and 5.6 µg/ml, respectively. Conclusion: The present study revealed a significant distribution of multidrug-resistant microbes, which may increase the burden of healthcare to prevent infections in cancer patients. Biosilver nanoparticles exhibit antimicrobial activity against multidrug-resistant microbes and could be considered as effective agents against these strains.