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1.
Spine (Phila Pa 1976) ; 47(19): 1337-1350, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094109

RESUMO

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to summarize recent literature on adult spinal deformity (ASD) treatment failure as well as prevention strategies for these failure modes. SUMMARY OF BACKGROUND DATA: There is substantial evidence that ASD surgery can provide significant clinical benefits to patients. The volume of ASD surgery is increasing, and significantly more complex procedures are being performed, especially in the aging population with multiple comorbidities. Although there is potential for significant improvements in pain and disability with ASD surgery, these procedures continue to be associated with major complications and even outright failure. METHODS: A systematic search of the PubMed database was performed for articles relevant to failure after ASD surgery. Institutional review board approval was not needed. RESULTS: Failure and the potential need for revision surgery generally fall into 1 of 4 well-defined phenotypes: clinical failure, radiographic failure, the need for reoperation, and lack of cost-effectiveness. Revision surgery rates remain relatively high, challenging the overall cost-effectiveness of these procedures. CONCLUSION: By consolidating the key evidence regarding failure, further research and innovation may be stimulated with the goal of significantly improving the safety and cost-effectiveness of ASD surgery.


Assuntos
Procedimentos Neurocirúrgicos , Análise Custo-Benefício , Reoperação , Falha de Tratamento
3.
Artigo em Inglês | MEDLINE | ID: mdl-36074445

RESUMO

Despite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.


Assuntos
Hepatite C Crônica , Sofosbuvir , Adulto , Antivirais/efeitos adversos , Estudos de Coortes , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Falha de Tratamento , Resultado do Tratamento
4.
Turk J Pediatr ; 64(4): 648-657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082639

RESUMO

BACKGROUND: High-flow nasal cannula (HFNC) therapy is a relatively new method used in patients with respiratory distress. The aim of the study was to evaluate the outcomes and to determine the baseline predictors of HFNC treatment failure in children with acute respiratory distress/failure in the pediatric emergency department. METHODS: Children with respiratory distress/failure aged 1 month to 18 years who underwent HFNC therapy with the pre-established protocol were retrospectively analyzed. HFNC therapy was used in respiratory and non-respiratory pathologies. HFNC failure was defined as the need for escalation to non-invasive ventilation or invasive mechanical ventilation. HFNC responders and non-responders were compared based on baseline clinical data. RESULTS: Of the 524 cases (median age:13 months; 292 males / 232 females), 484 (92.4%) had respiratory tract and 40 (7.6%) had non-respiratory tract pathologies. HFNC therapy was unsuccessful in 62 (11.8%) patients. The success rates were 81% and 55% in respiratory and non-respiratory diseases, respectively. In children with respiratory system pathologies, the pre-treatment venous pCO2 level (p: 0.045; OR: 0.958; 95%CI: 0.821-0.990) and the clinically important radiological finding on chest X-ray (lobar infiltration, atelectasis, pleural effusion) (p: 0.045; OR: 3.262; 95%CI: 1.178-9.034) were the most significant parameters in predicting HFNC failure. In children with non-respiratory pathologies, the pre-treatment venous lactate level (p: 0.008; OR: 1.558; 95%CI: 1.125-2.158) was a significant predictor of HFNC failure. There were no cases of pneumothorax or any other reported adverse effects related to HFNC therapy. CONCLUSIONS: HFNC treatment is a safe oxygen therapy in children with respiratory distress/failure due to various etiologies in the emergency department. The lower venous pCO2 level increases and the clinically important radiological finding on chest radiograph decreases the success of HFNC treatment in respiratory pathologies. The higher venous lactate level is a predictor of HFNC treatment failure in non-respiratory pathologies.


Assuntos
Ventilação não Invasiva , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Cânula , Criança , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Lactatos , Masculino , Oxigênio , Oxigenoterapia/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Falha de Tratamento
5.
Biomed Pharmacother ; 149: 112874, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36068770

RESUMO

The western Amazon basin is an important endemic area for malaria by P. vivax. In recent years, several reports showed the treatment failure with chloroquine, which can be related to resistance. The assessment of chloroquine resistance requires the evaluation of drug exposure, and when possible, the estimation of the pharmacokinetic parameters. However, there is no data on the pharmacokinetics of chloroquine in this endemic area. Moreover, the influence of the early reappearance of parasites in blood on the exposure to the drug was low exploited in the literature. The present study described the pharmacokinetic parameters of chloroquine in whole blood of adult patients with P. vivax malaria from the western Brazilian Amazon basin and compared the area under the curve (AUC) with the parasitological outcome at day 28. A total of 19 patients with parasite recurrence within 28 days and 20 patients with no recurrence were included in the study. Chloroquine was measured by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters were estimated by non-compartmental modeling. The maximum concentration ranged from 1285 to 2030 ng/mL. The terminal half-life varied from 5.3 to 12.8 days. The volume of distribution from 1090 to 2340 L/kg, and the area under the curve to the last measurable concentration from 247 to 432 ng/mL.h. The pharmacokinetic parameters were similar in both groups, which suggests the lack of influence of early reappearance of parasites on chloroquine pharmacokinetics.


Assuntos
Antimaláricos , Malária Vivax , Adulto , Antimaláricos/farmacologia , Brasil , Cloroquina/farmacocinética , Cloroquina/uso terapêutico , Resistência a Medicamentos , Humanos , Malária Vivax/induzido quimicamente , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Plasmodium vivax , Falha de Tratamento
6.
Int J Clin Pract ; 2022: 7518971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120665

RESUMO

Purpose: Insertion of a ureteral access sheath (UAS) may fail in some patients in retrograde intrarenal surgery (RIRS), and this study aimed to seek preoperative risk factors for the failure of 12/14F UAS placement. Methods: We retrospectively analyzed 260 consecutive patients who underwent RIRS between May 2020 and March 2022 at our institution. Data on patient and stone characteristics and several computed tomography (CT)-based measurements were collected and compared between the success and failure UAS placement groups. Results: Twenty-nine (11.2%) patients failed to insert the UAS. Age, gender, height, weight, stone side, stone location, length of history, and computed tomography (CT)-based parameters were not significant differences between the two groups. Univariate logistic regression analyses showed sex (female/male) (odds ratio: 0.287 and 95% CI [0.107, 0.722], p=0.013), length of history 15-31 days (odds ratio: 0.315 and 95% CI [0.102, 0.974], p=0.045), length of history >31 days (odds ratio: 0.202 and 95% CI [0.051, 0.805], p=0.023), and diameter of the ipsilateral common iliac artery (odds ratio: 1.285 and 95% CI [1.018, 1.623], p=0.035) were associated with UAS placement. Conclusion: Our study indicated that males, the short length of history, and the short diameter of the ipsilateral common iliac artery were the risk factors for the failure of UAS placement.


Assuntos
Cálculos Renais , Ureter , Feminino , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Masculino , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Ureter/diagnóstico por imagem , Ureter/cirurgia
7.
BMC Pulm Med ; 22(1): 358, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127681

RESUMO

BACKGROUND: Pleural infection is an infection of the pleural space that is usually treated with antibiotics and source control. Chest tube insertion is the most popular and widely used drainage technique. We typically attempt to place the tube at the bottom of the thoracic cavity to consider the effects of gravity; however, the effectiveness of this practice is not well-defined. Therefore, we aimed to examine whether the position of the tip of the thoracic tube affects treatment failure in patients with pleural infection. METHODS: In this retrospective observational study, patients with pleural infection who underwent thoracic tube insertion were divided into two groups: those with the tip of the tube positioned below the 10th thoracic vertebra at the level of the diaphragm (lower position group) and those with the tip placed above the 9th thoracic vertebra (upper position group). We compared whether the position of the tube tip affected treatment failure. Stabilized inverse probability treatment weights (SIPTW) were used to balance the baseline characteristics between the groups. Treatment failure showed a composite outcome of hospital death, referral to surgeons for surgery, and additional chest tube insertion. RESULTS: Among the 87 patients, 41 and 46 patients were in the lower and upper groups, respectively. No significant difference was observed in the composite outcomes between the groups (46.3% vs. 54.3%, P = 0.596). There was also no significant difference in the composite outcome between both groups after adjusting for SIPTW (52.3% vs. 68.8%, P = 0.286). CONCLUSIONS: There were no significant differences in the treatment failure in this study addressing pleural infection treatment, in which the drain tip position was stratified by the 9th and 10th thoracic vertebrae. The position of the tip of the thoracic tube may not be important for pleural infection treatment providing that it is in the thoracic cavity. Trial registration The participants were registered retrospectively.


Assuntos
Tubos Torácicos , Doenças Pleurais , Tubos Torácicos/efeitos adversos , Humanos , Cavidade Pleural , Estudos Retrospectivos , Falha de Tratamento
8.
J Headache Pain ; 23(1): 105, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36071388

RESUMO

OBJECTIVE: The relative effects of monoclonal antibody against calcitonin gene-related peptide (CGRP) or its receptor for adult migraine patients with prior treatment failure remains uncertain. Therefore, this study systematically assessed the comparative effectiveness of different CGRP binding monoclonal antibodies (mAbs) for these patients. METHODS: Several online databases including Ovid MEDILNE, Ovid EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to June 15, 2022. We included randomized clinical trials (RCT) of adult migraine patients with previous treatment failure that assessed any CGRP monoclonal antibody. The primary efficacy outcome was change in monthly migraine days (MMDs), and the primary safety outcome was treatment-emergent adverse events (TEAEs). RESULTS: Overall, seven studies totaling 3, 052 patients were included. Three-node analysis showed that CGRP mAbs was superior to CGRP receptor mAbs in reducing MMDs (MD: -1.55, 95% CrI: - 2.43 to - 0.44) and improving at least 50% response rates (RR: 1.52, 95% CrI: 1.04 to 2.21). Nine-node analysis showed galcanezumab 240 mg ranked first in reducing MMDs (MD -4.40, 95% CrI - 7.60 to - 1.19) and improving 50% response rates (RR: 4.18, 95% CrI: 2.63 to 6.67). Moreover, treatment with fremanezumab or eptinezumab 300 mg provides a significant advantage over erenumab 140 mg regarding an improved response rate of at least 50%. The analysis did not show difference in incidences of TEAEs and serious adverse events in any of the comparisons. CONCLUSIONS: It appears that CGRP mAbs, especially galcanezumab 240 mg, monthly fremanezumab, and eptinezumab 300 mg, seem to be the best choice for the treatment of migraine patients with previous treatment failures. This finding also calls for future research that examine the associations between these medications in migraine therapy among the same patient group to testify the present findings.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Adulto , Anticorpos Monoclonais/efeitos adversos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Humanos , Transtornos de Enxaqueca/metabolismo , Metanálise em Rede , Falha de Tratamento
9.
J Int AIDS Soc ; 25(8): e25989, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36028921

RESUMO

INTRODUCTION: Viral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second-line regimen. METHODS: Among 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median < 0.80 was classified into the non-routine VL sites. VF was defined as VL ≥1000 copies/ml during first-line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution. RESULTS: Of 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non-routine VL testing sites. The median follow-up was 9 years (IQR 5-13). The median age was 35 (30-42) years; 68% were male and 5729 (91%) started non-nucleoside reverse-transcriptase inhibitor-based regimen. The median pre-ART CD4 count in PLHIV from routine VL sites was lower compared to non-routine VL sites (144 vs. 156 cells/mm3 , p <0.001). Overall, 1021 subsequent VF at a rate of 2.15 (95% CI 2.02-2.29) per 100 person-years (PY). VF was more frequent at non-routine VL sites (adjusted incidence rate ratio 2.85 [95% CI 2.27-3.59]) compared to routine VL sites. Other factors associated with an increased rate of VF were age <50 years and CD4 count <350 cells/mm3 . A total of 817 (13%) patients switched to second-line regimen at a rate of 1.44 (95% CI 1.35-1.54) per 100 PY. PLHIV at routine VL monitoring sites were at higher risk of switching than those at non-routine VL sites (adjusted sub-hazard ratio 1.78 95% CI [1.17-2.71]). CONCLUSIONS: PLHIV from non-routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under-utilized VL testing.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Carga Viral
10.
J Mol Model ; 28(9): 260, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35984530

RESUMO

Scientific pieces of evidence indicate that the polymorphism in the ALR2 regulatory gene favors the susceptibility to diabetic complications (DCs). Previous studies have uncovered several single nucleotide polymorphisms (SNPs) in the ALR2 regulatory sites that negatively modulate the activity of this enzyme and eventually increase the risks of DCs. In view of this, the current study aimed at investigating whether the mutation as a resultant of missense SNPs in the regulatory site of ALR2 enzyme can also hamper the interactions of ALR2 inhibitors with the key amino acid residues in the ALR2 binding site. Around 202 SNPs in the ALR2 gene were reported in the dbSNP database. Out of these, eighteen SNPs that are responsible for point mutations in the regulatory sites of ALR2 enzyme were identified and considered for the study. Identified SNPs were then categorized as stabilizing or destabilizing using various in silico tools and webservers. The resulting mutational constructs of ALR2 were further probed for their influence on the binding affinities and binding modes with well-known ALR2 inhibitors using structure-based analyses. This study identified three destabilizing SNPs, i.e., rs779176563 (C298S), rs1392886142 (G16A), and rs1407261115 (A245T), that lead to the compromised response to most of the ALR2 inhibitors which are in clinical trials. On the other hand, treatment with these ALR2 inhibitors may benefit the population which carries missense SNPs rs748119899, rs1402962430, and rs1467939858 that code for W219S, Q183V, and S214A, respectively. Overall findings of the study suggest that one SNP in the inhibitor site and two SNPs in the co-factor site of ALR2 may be responsible for the low efficacy and unsuccessful journey of ALR2 inhibitors in the clinical trials.


Assuntos
Aldeído Redutase , Complicações do Diabetes , Diabetes Mellitus , Aldeído Redutase/genética , Aldeído Redutase/metabolismo , Complicações do Diabetes/genética , Diabetes Mellitus/genética , Inibidores Enzimáticos/farmacologia , Humanos , Mutação , Polimorfismo de Nucleotídeo Único , Falha de Tratamento
13.
N Z Med J ; 135(1559): 118-121, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35999787

RESUMO

Paradoxical reactions are immune-mediated disease exacerbations that can occur in Mycobacterium tuberculosis (TB) following initiation of treatment. They are rare, challenging to manage and often fatal. We present a case of neurotuberculosis in a young woman, complicated by a paradoxical reaction in which infliximab was trialled without success. This case demonstrates the severity of presentation that can occur in neurotuberculosis, and the complications that paradoxical reactions can present. It also highlights the difficulty of delivering palliative care within the context of communicable disease with challenges posed by both TB and the COVID-19 pandemic.


Assuntos
Infliximab , Tuberculose do Sistema Nervoso Central , Feminino , Humanos , Infliximab/uso terapêutico , Mycobacterium tuberculosis , Nova Zelândia , Pandemias , Falha de Tratamento , Tuberculose do Sistema Nervoso Central/tratamento farmacológico
14.
Crit Care ; 26(1): 196, 2022 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-35786223

RESUMO

BACKGROUND: Heart rate, acidosis, consciousness, oxygenation, and respiratory rate (HACOR) have been used to predict noninvasive ventilation (NIV) failure. However, the HACOR score fails to consider baseline data. Here, we aimed to update the HACOR score to take into account baseline data and test its predictive power for NIV failure primarily after 1-2 h of NIV. METHODS: A multicenter prospective observational study was performed in 18 hospitals in China and Turkey. Patients who received NIV because of hypoxemic respiratory failure were enrolled. In Chongqing, China, 1451 patients were enrolled in the training cohort. Outside of Chongqing, another 728 patients were enrolled in the external validation cohort. RESULTS: Before NIV, the presence of pneumonia, cardiogenic pulmonary edema, pulmonary ARDS, immunosuppression, or septic shock and the SOFA score were strongly associated with NIV failure. These six variables as baseline data were added to the original HACOR score. The AUCs for predicting NIV failure were 0.85 (95% CI 0.84-0.87) and 0.78 (0.75-0.81) tested with the updated HACOR score assessed after 1-2 h of NIV in the training and validation cohorts, respectively. A higher AUC was observed when it was tested with the updated HACOR score compared to the original HACOR score in the training cohort (0.85 vs. 0.80, 0.86 vs. 0.81, and 0.85 vs. 0.82 after 1-2, 12, and 24 h of NIV, respectively; all p values < 0.01). Similar results were found in the validation cohort (0.78 vs. 0.71, 0.79 vs. 0.74, and 0.81 vs. 0.76, respectively; all p values < 0.01). When 7, 10.5, and 14 points of the updated HACOR score were used as cutoff values, the probability of NIV failure was 25%, 50%, and 75%, respectively. Among patients with updated HACOR scores of ≤ 7, 7.5-10.5, 11-14, and > 14 after 1-2 h of NIV, the rate of NIV failure was 12.4%, 38.2%, 67.1%, and 83.7%, respectively. CONCLUSIONS: The updated HACOR score has high predictive power for NIV failure in patients with hypoxemic respiratory failure. It can be used to help in decision-making when NIV is used.


Assuntos
Ventilação não Invasiva , Insuficiência Respiratória , Humanos , Unidades de Terapia Intensiva , Ventilação não Invasiva/métodos , Estudos Prospectivos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Falha de Tratamento
15.
Folia Med (Plovdiv) ; 64(3): 422-429, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35856103

RESUMO

INTRODUCTION: Mycoplasmagenitalium is an established cause of sexually transmitted infections in men and women. Current guidelines recommend azithromycin and moxifloxacin as first- and second-line treatment, respectively. However, azithromycin treatment failure has been increasingly reported. The aim of this study was to determine the efficacy of azithromycin and alternative antibiotic regimens in a prospective cohort of M.genitalium-positive patients, and macrolide resistance mutations associated with azithromycin failure.


Assuntos
Infecções por Mycoplasma , Mycoplasma genitalium , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Bulgária , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Masculino , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/genética , Estudos Prospectivos , Falha de Tratamento
16.
Neuromodulation ; 25(5): 775-782, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35803682

RESUMO

OBJECTIVE: Spinal cord stimulation (SCS) has become a popular nonopioid pain intervention. However, the treatment failure rate for SCS remains significantly high and many of these patients have poor sagittal spinopelvic balance, which has been found to correlate with increased pain and decreased quality of life. The purpose of this study was to determine if poor sagittal alignment is correlated with SCS treatment failure. MATERIALS AND METHODS: Comparative retrospective analysis was performed between two cohorts of patients who had undergone SCS placement, those who had either subsequent removal of their SCS system (representing a treatment failure cohort) and those that underwent generator replacement (representing a successful treatment cohort). The electronic medical record was used to collect demographic and surgical characteristics, which included radiographic measurements of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Also included were data on pain medication usage including opioid and nonopioid therapies. RESULTS: Eighty-one patients met inclusion criteria, 31 had complete removal, and 50 had generator replacements. Measurement of sagittal balance parameters demonstrated that many patients had poor alignment, with 34 outside normal range for LL (10 vs 24 in removal and replacement cohorts, respectively), 30 for PI (12 [38.7%] vs 18 [36.0%]), 46 for PT (18 [58.1%] vs 28 [56.0%]), 38 for SS (18 [58.1%] vs 20 [40.0%]), and 39 for PI-LL mismatch (14 [45.2%] vs 25 [50.0%]). There were no significant differences in sagittal alignment parameters between the two cohorts. CONCLUSIONS: This retrospective cohort analysis of SCS patients did not demonstrate any relationship between poor sagittal alignment and failure of SCS therapy. Further studies of larger databases should be performed to determine how many patients ultimately go on to have additional structural spinal surgery after failure of SCS and whether or not those patients go on to have positive outcomes.


Assuntos
Lordose , Vértebras Lombares , Estimulação da Medula Espinal , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Dor/prevenção & controle , Pelve , Qualidade de Vida , Estudos Retrospectivos , Medula Espinal , Falha de Tratamento
17.
Front Immunol ; 13: 904497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874685

RESUMO

Immunotherapy with T cells genetically modified with chimeric antigen receptors (CARs) has shown significant clinical efficacy in patients with relapsed/refractory B-cell lymphoma. Nevertheless, more than 50% of treated patients do not benefit from such therapy due to either absence of response or further relapse. Elucidation of clinical and biological features that would predict clinical response to CART19 therapy is of paramount importance and eventually may allow for selection of those patients with greater chances of response. In the last 5 years, significant clinical experience has been obtained in the treatment of diffuse large B-cell lymphoma (DLBCL) patients with CAR19 T cells, and major advances have been made on the understanding of CART19 efficacy mechanisms. In this review, we discuss clinical and tumor features associated with response to CART19 in DLBCL patients as well as the impact of biological features of the infusion CART19 product on the clinical response. Prognosis of DLBCL patients that fail CART19 is poor and therapeutic approaches with new drugs are also discussed.


Assuntos
Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia , Linfócitos T , Falha de Tratamento
18.
J Int Assoc Provid AIDS Care ; 21: 23259582221111080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844136

RESUMO

Background: The function of antiretroviral therapy is to enhance immunity and prevent the occurrence of opportunistic infection. But antiretroviral therapy showed a failure to manage infection after a time. Nowadays, an accepted criterion to confirm Antiretroviral therapy (ART) treatment failure is a virologic failure. Regarding this virologic failure, there are no well-addressed findings, especially in this study area. Therefore in this research, the magnitude and factors that contribute for virological ART treatment failure have been identified. Methods: Facilitybased cross-sectional study was conducted on adult patients taking ART. Data entry was conducted using Epi Data Version3 and exported to Stata SE version 14 for analysis. Bivariable logistic regression was used to find covariates significantly associated with firs line ART treatment failure. In this case, variables with P-value ≤ .25 were a candidate for multiple logistic regressions. A backward logistic regression model was used. Finally, variables with P-value ≤ .05 were considered as factors significantly associated with first-line ART treatment failure and the result was presented with a description, graph, and tables. Results: In this study, three hundred and fifty peoples were a candidate for the study and all have been involved. The magnitude of first-line ART treatment failure based on virologic criteria was 20.85%. Greater than three-fourth (84.29%) of study participants have support from somebody. Those patients who have initiated first-line ART with NVP based regimen have 1.83 times more likely to face first-line ART treatment failure as compared with those who have started with Efeverence (EFV) based regimen [AOR = 1.83, 95% CI (1.035, 3.245)]. Patients who have initiated first-line ART at the health center were 3.093 times more likely to face first-line ART treatment failure as compared those who have initiated ART at hospitals [AOR = 3.093, 95% CI (1.101, 8.685)]. Patients who have not developed a common opportunistic infection after ART initiation was 47.3% less likely to encounter first-line ART treatment failure as compared with those who have opportunistic infection [AOR = 0.527, 95% CI (0.289, 0.961)]. Conclusion: Based on virologic criteria, NVP based ART initiation, having history recorded opportunistic infection after ART initiation, being male, Institution where initiate ART, are significantly associated with the occurrences of first-line ART treatment failure. The action has to be directed on those identified factors to maintain the patient stay on First-line ART by concerned stakeholders.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , Infecções Oportunistas , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Etiópia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Soropositividade para HIV/tratamento farmacológico , Humanos , Masculino , Infecções Oportunistas/tratamento farmacológico , Falha de Tratamento
19.
J Int Assoc Provid AIDS Care ; 21: 23259582221110454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35854413

RESUMO

HIV drug resistance is an emerging public health concern; appropriate ART combinations and safe drug switches are prerequisites for achieving virologic suppression. In the early 2000, in Sub-Saharan Africa, accent was mostly on prevention and the scale up of Antiretroviral therapy has just initiated. We report a 46-year-old female who was initiated on ART in 2005 in the private sector, had multiple regimens changes for unclear reasons. Over 7 years (2005-2012), she deteriorated and presented with an AIDS defining condition. A genotyping resistance test (GRT) revealed multiple HIV class resistance and was switched to a third-line ART and improved on treatment. This case report shows that the absence of formal ART guidelines in early 2000, long term exposure to ART and failure to timely switch led to treatment failure and development of multiclass drug resistance mutations identified by the HIV-1 GRT and guided the third-line ART regimen with a successful outcome.


Assuntos
Síndrome de Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Resistência a Medicamentos , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Pessoa de Meia-Idade , Falha de Tratamento , Carga Viral
20.
Ann Palliat Med ; 11(6): 2100-2109, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35817745

RESUMO

BACKGROUND: The treatment of lung cancer patients, especially those with epidermal growth factor receptor (EGFR)-mutant T790M-negative adenocarcinoma, after first- or second-line tyrosine kinase inhibitor (TKI) treatment failure is challenging due to the poor prognosis and limited effectiveness of platinum two-drug chemotherapy or chemotherapy plus anti-angiogenesis therapy. It is well-known that pembrolizumab monotherapy exhibits low toxicity and long-term survival, but it is unknown in these patients. METHODS: From September 2018 to March 2021, 460 patients in Jiangmen Central Hospital were included and 82 patients with disease progression in lung adenocarcinoma who remained T790M-negative on the second biopsy were screened. Two groups were divided according to treatment status, and simple random sampling was performed to obtain 32 cases respectively. The safety of the patients was subsequently evaluated by telephone follow-up. RESULTS: The objective response rate (ORR) and disease control rate (DCR) in the pembrolizumab group were 15.63% and 53.13%. In the chemotherapy group, the ORR was 8.33% and the DCR was 25% (P<0.05). In the pembrolizumab group, the progression-free survival (PFS) [14.65 months, 95% confidence interval (CI): 13.03 to 16.28] was significantly higher than that of the control group (9.54 months, 95% CI: 8.43 to 10.65) (P<0.05). In the univariate analysis, programmed cell death protein 1 ligand (PD-L1) expression, smoking status, gender, and whether first-line chemotherapy was associated with survival. In the multivariate analysis, gender [P=0.001; hazard ratio (HR) 10.98, 95% CI: 2.49-46.67], first-line chemotherapy (P=0.037; HR 4.5, 95% CI: 1.1-4.81), and PD-L1 expression (P=0.039; HR 0.16, 95% CI: 0.04-0.68) were correlated with patient survival. Grade 3 or grade 4 treatment-related adverse events were not found in the pembrolizumab group, while 2 cases of grade 3 or 4 treatment-related adverse events occurred in the control group. CONCLUSIONS: In advanced lung adenocarcinoma patients with EGFR-mutant T790M-negative after TKI treatment, pembrolizumab had a higher ORR and PFS. Pembrolizumab in women with first-line chemotherapy and PD-L1 ≥25% of those patients may have a good response and a low rate of adverse reactions. A multicenter, prospective, evidence-based study of pembrolizumab salvage therapy in those patients is warranted for posterior line treatment.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Pemetrexede/uso terapêutico , Platina/uso terapêutico , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Falha de Tratamento
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