-
Cancer Research and Treatment Jul 2023We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis. (Meta-Analysis)
Meta-Analysis
Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis.
PURPOSE
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
MATERIALS AND METHODS
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
RESULTS
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
CONCLUSION
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.
Topics: Humans; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols; Salvage Therapy; Neoplasm Recurrence, Local; Hematopoietic Stem Cell Transplantation; Lymphoma, Large B-Cell, Diffuse
PubMed: 36915243
DOI: 10.4143/crt.2022.1658 -
The International Journal of... Apr 2020Resistant bipolar disorder is a major mental health problem related to significant disability and overall cost. The aim of the current study was to perform a systematic...
BACKGROUND
Resistant bipolar disorder is a major mental health problem related to significant disability and overall cost. The aim of the current study was to perform a systematic review of the literature concerning (1) the definition of treatment resistance in bipolar disorder, (2) its clinical and (3) neurobiological correlates, and (4) the evidence-based treatment options for treatment-resistant bipolar disorder and for eventually developing guidelines for the treatment of this condition.
MATERIALS AND METHODS
The PRISMA method was used to identify all published papers relevant to the definition of treatment resistance in bipolar disorder and the associated evidence-based treatment options. The MEDLINE was searched to April 22, 2018.
RESULTS
Criteria were developed for the identification of resistance in bipolar disorder concerning all phases. The search of the literature identified all published studies concerning treatment options. The data were classified according to strength, and separate guidelines regarding resistant acute mania, acute bipolar depression, and the maintenance phase were developed.
DISCUSSION
The definition of resistance in bipolar disorder is by itself difficult due to the complexity of the clinical picture, course, and treatment options. The current guidelines are the first, to our knowledge, developed specifically for the treatment of resistant bipolar disorder patients, and they also include an operationalized definition of treatment resistance. They were based on a thorough and deep search of the literature and utilize as much as possible an evidence-based approach.
Topics: Anticonvulsants; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Drug Resistance; Evidence-Based Medicine; Humans; Practice Guidelines as Topic
PubMed: 31802122
DOI: 10.1093/ijnp/pyz064 -
Pediatric Blood & Cancer Mar 2023Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children... (Review)
Review
Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Blood Platelets; Treatment Outcome; Consensus
PubMed: 36579787
DOI: 10.1002/pbc.30173 -
Journal of Cardiac Surgery Oct 2021Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased...
BACKGROUND
Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased cardiac index, and characterized by inadequate response to standard doses of vasopressors, and increased morbidity and mortality. It occurs in 9%-44% of cardiac surgery patients after cardiopulmonary bypass (CPB). The underlying pathophysiology following CPB consists of resistance to vasopressors (inactivation of Ca voltage gated channels) on the one hand and excessive activation of vasodilators (SIRS, iNOS, and low AVP) on the other. Use of angiotensin-converting enzyme inhibitor (ACE-I), calcium channel blockers, amiodarone, heparin, low cardiac reserve (EF < 35%), symptomatic congestive heart failure, and diabetes mellitus are the perioperative risk factors for VPS after cardiac surgery in adults. Till date, there is no consensus about the outcome-oriented therapeutic management of VPS. Vasopressors such as norepinephrine (NE; 0.025-0.2 µg/kg/min) and vasopressin (0.06 U/min or 6 U/h median dose) are the first choice for the treatment. The adjuvant therapy (hydrocortisone, calcium, vitamin C, and thiamine) and rescue therapy (methylene blue [MB] and hydroxocobalamin) are also considered when perfusion goals (meanarterial pressure [MAP] > 60-70 mmHg) are not achieved with nor-epinephrine and/or vasopressin.
AIMS
The aims of this systematic review are to collect all the clinically relevant data to describe the VPS, its potential risk factors, pathophysiology after CPB, and to assess the efficacy, safety, and outcome of the therapeutic management with catecholamine and non-catecholamine vasopressors employed for refractory vasoplegia after cardiac surgery. Also, to elucidate the current and practical approach for management of VPS after cardiac surgery.
MATERIAL AND METHODS
"PubMed," "Google," and "Medline" weresearched, and over 150 recent relevant articles including RCTs, clinical studies, meta-analysis, reviews, case reports, case series and Cochrane data were analyzed for this systematic review. The filter was applied specificallyusing key words like VPS after cardiac surgery, perioperative VPS following CPB, morbidity, and mortality in VPS after cardiac surgery, vasopressors for VPS that improve outcomes, VPS after valve surgery, VPS after CABG surgery, VPS following complex congenital cardiac anomalies corrective surgery, rescue therapy for VPS, adjuvant therapy for VPS, definition of VPS, outcome in VPS after cardiac surgery, etiopathology of VPS following CPB. This review did not require any ethical approval or consent from the patients.
RESULTS
Despite the recent advances in therapy, the mortality remains as high as 30%-50%. NE has been recommended the most frequent used vasopressor for VPS. It restores and maintain the MAP and provides the outcome benefits. Vasopressin rescue therapy is an alternative approach, if catecholamines and fluid infusions fail to improve hemodynamics. It effectively increases vascular tone and lowers CO, and significantly decreases the 30 days mortality. Hence, suggested a first-line vasopressor agent in postcardiac surgery VPS. Terlipressin (1.3μg/kg/h), a longer acting and more specific vasoconstrictor prevents the development of VPS after CPB in patients treated with ACE-I. MB significantly reduces morbidity and mortality of VPS. The Preoperative MB (1%, 2mg/kg/30min, 1h before surgery) administration in high risk (on ACE-I) patients for VPS undergoing CABG surgery, provides 100% protection against VPS, and early of MB significantly reduces operative mortality, and recommended as a rescue therapy for VPS. Hydroxocobalamin (5 g) has been recommended as a rescue agent in VPS refractory to multiple vasopressors. A combination of ascorbic acid (6 g), hydrocortisone (200 mg/day), and thiamine (400 mg/day) as an adjuvant therapy significantly reduces the vasopressors requirement, and provides mortality and morbidity benefits.
CONCLUSION
Currently, the VPS is frequently encountered (9%-40%) in cardiac surgical patients with predisposing patient-specific risk factors and combined with inflammatory response to CPB. Multidrug therapy (NE, MB, AVP, ATII, terlipressin, hydroxocobalamin) targeting multiple receptor systems is recommended in refractory VPS. A combination of high dosage of ascorbic acid, hydrocortisone and thiamine has been used successfully as adjunctive therapyto restore the MAP. We also advocate for the early use of multiagent vasopressors therapy and catecholamine sparing adjunctive agents to restore the systemic perfusion pressure with a goal of preventing the progressive refractory VPS.
Topics: Adult; Cardiopulmonary Bypass; Drug Therapy, Combination; Humans; Hydroxocobalamin; Leprostatic Agents; Vasoplegia
PubMed: 34251716
DOI: 10.1111/jocs.15805 -
European Spine Journal : Official... Jul 2022Spondylodiscitis is a severe condition where standalone antibiotic therapy resolves most cases. In refractory infections, open surgery may aid with infection debulking.... (Review)
Review
BACKGROUND
Spondylodiscitis is a severe condition where standalone antibiotic therapy resolves most cases. In refractory infections, open surgery may aid with infection debulking. However, significant morbidity can occur. Nowadays, endoscopic approaches are emerging as an alternative. However, until now, only small-scale studies exist. Being so, we carried the first systematic review on spondylodiscitis endoscopic debridement indications, technique details, and outcomes.
METHODS
Search for all English written original studies approaching the spondylodiscitis endoscopic treatment was performed using PubMed and EBSCO host. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a pre-specified protocol was registered at PROSPERO (CRD42020183657).
RESULTS
Fourteen studies involving 342 participants were included for analysis. Data overall quality was fair. Indications for the endoscopic approach were poorly defined. The most consensual indication was refractory infection to conservative treatment. Spinal instability or neurological deficits were common exclusion criteria. All authors described similar techniques, and despite the frequent severe co-morbidities, procedure morbidity was low. Re-interventions were common. Microorganism identification varied from 54.2 to 90.4%. Treatment failure among studies ranged from 0 to 33%. Pain, functional status, and neurological deficits had satisfactory improvement after procedures.
CONCLUSIONS
The endoscopic debridement of spondylodiscitis seems to be an effective and safe approach for refractory spondylodiscitis. A novel approach with initial endoscopic infection debulking and antibiotic therapy could improve the success of spondylodiscitis treatment.
Topics: Anti-Bacterial Agents; Debridement; Discitis; Endoscopy; Humans; Lumbar Vertebrae; Retrospective Studies; Spinal Diseases; Treatment Outcome
PubMed: 35211807
DOI: 10.1007/s00586-022-07142-w -
Neurosurgical Focus Feb 2023Despite its relatively low prevalence, schizophrenia has a high burden of illness due to its lifelong effects and the fact that it is often refractory to psychotropic...
OBJECTIVE
Despite its relatively low prevalence, schizophrenia has a high burden of illness due to its lifelong effects and the fact that it is often refractory to psychotropic treatment. This review investigated how neurosurgical interventions, primarily neuromodulation through deep brain stimulation (DBS), can mitigate treatment-refractory schizophrenia. Pathophysiological data and ongoing clinical trials were reviewed to suggest which targets hold promise for neurosurgical efficacy.
METHODS
A systematic review of the literature was conducted via an electronic search of the PubMed, Scopus, and Web of Science databases. Included papers were human or animal studies of neurosurgical interventions for schizophrenia conducted between 2012 and 2022. An electronic search of ClinicalTrials.gov and the International Clinical Trials Registry Platform was conducted to find ongoing clinical trials. The ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) assessment tool was used to evaluate risk of bias in the study.
RESULTS
Eight human and 2 rat studies were included in the review. Of the human studies, 5 used DBS targeting the nucleus accumbens, subgenual anterior cingulate cortex, habenula, and substantial nigra pars reticulata. The remaining 3 human studies reported the results of subcaudate tractotomies and anterior capsulotomies. The rat studies investigated DBS of the nucleus accumbens and medial prefrontal cortex. Overall, human studies demonstrated long-term reduction in Positive and Negative Syndrome Scale scores in many participants, with a low incidence of surgical and psychological side effects. The rat studies demonstrated improved prepulse and latent inhibition in the targeted areas after DBS.
CONCLUSIONS
As identified in this review, recent studies have investigated the potential effects of therapeutic DBS for schizophrenia, with varying results. DBS targets that have been explored include the hippocampus, subgenual anterior cingulate cortex, habenula, substantia nigra pars reticulata, and medial prefrontal cortex. In addition to DBS, other neuromodulatory techniques such as neuroablation have been studied. Current evidence suggests that neuroablation in the subcaudate tract and anterior capsulotomy may be beneficial for some patients. The authors recommend further exploration of neuromodulation for treatment-refractory schizophrenia, under the condition that rigorous standards be upheld when considering surgical candidacy for these treatments, given that their safety and efficacy remain to be determined.
Topics: Humans; Rats; Animals; Schizophrenia; Neurosurgery; Neurosurgical Procedures; Psychosurgery; Nucleus Accumbens; Deep Brain Stimulation
PubMed: 36724524
DOI: 10.3171/2022.11.FOCUS22620 -
Frontiers in Neurology 2023New-onset refractory status epilepticus (NORSE) and its subset of febrile infection-related epilepsy syndrome (FIRES) are devastating clinical presentations with high...
BACKGROUND
New-onset refractory status epilepticus (NORSE) and its subset of febrile infection-related epilepsy syndrome (FIRES) are devastating clinical presentations with high rates of mortality and morbidity. The recently published consensus on the treatment of these conditions includes anesthetics, antiseizure drugs, antivirals, antibiotics, and immune therapies. Despite the internationally accepted treatment, the outcome remains poor for a significant percentage of patients.
METHODS
We conducted a systematic review of the use of neuromodulation techniques in the treatment of the acute phase of NORSE/FIRES using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Our search strategy brought up 74 articles of which 15 met our inclusion criteria. A total of 20 patients were treated with neuromodulation. Thirteen cases represented FIRES and in 17 cases the NORSE remained cryptogenic. Ten had electroconvulsive therapy (ECT), seven had vagal nerve stimulation (VNS), and four had deep brain stimulation (DBS); one patient had initially VNS and later DBS. Eight patients were female and nine were children. In 17 out of 20 patients, the status epilepticus was resolved after neuromodulation, while three patients died.
CONCLUSION
NORSE can have a catastrophic course and the first treatment goal should be the fastest possible termination of status epilepticus. The data presented are limited by the small number of published cases and the variability of neuromodulation protocols used. However, they show some potential clinical benefits of early neuromodulation therapy, suggesting that these techniques could be considered within the course of FIRES/NORSE.
PubMed: 37388544
DOI: 10.3389/fneur.2023.1195844 -
World Journal of Gastroenterology Jan 2023Due to increasing resistance rates of () to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and...
BACKGROUND
Due to increasing resistance rates of () to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and treatment algorithms for first-line and second-line therapy against infection are well-established, there is no clear recommendation for third-line and rescue therapy in refractory infection.
AIM
To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory infection.
METHODS
A systematic search of available rescue treatments for refractory infection was conducted on the National Library of Medicine's PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of infection rescue therapies were included.
RESULTS
Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for analysis of mean eradication rate as third-line treatment. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple-therapy as third-line treatment, mean eradication rates of 81.6% and 84.4%, 79.4% and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. For third-line quadruple therapy, mean eradication rates of 69.2% and 72.1% were found for bismuth quadruple therapy (BQT), 88.9% and 90.9% for bismuth quadruple therapy, three-in-one, Pylera (BQT-Pylera), and 61.3% and 64.2% for non-BQT) in ITT and PP analysis, respectively. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple therapy as rescue therapy, mean eradication rates of 75.4% and 78.8%, 79.4 and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in ITT and PP analysis, respectively. For quadruple therapy as rescue treatment, mean eradication rates of 76.7% and 79.2% for BQT, 84.9% and 87.8% for BQT-Pylera, and 61.3% and 64.2% for non-BQT were found in ITT and PP analysis, respectively. For susceptibility-guided therapy, mean eradication rates as third-line and rescue treatment were 75.0% in ITT and 79.2% in PP analysis.
CONCLUSION
We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile. In regions with known resistance to macrolides or unavailability of bismuth, rifabutin-based triple therapy is recommended.
Topics: Humans; Helicobacter Infections; Anti-Bacterial Agents; Metronidazole; Helicobacter pylori; Bismuth; Levofloxacin; Proton Pump Inhibitors; Drug Therapy, Combination; Macrolides; Drug Resistance, Bacterial; Tetracycline; Rifabutin
PubMed: 36687120
DOI: 10.3748/wjg.v29.i2.390 -
European Spine Journal : Official... Jan 2022We sought to systematically assess and summarize the available literature on outcomes following coccygectomy for refractory coccygodynia. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We sought to systematically assess and summarize the available literature on outcomes following coccygectomy for refractory coccygodynia.
METHODS
PubMed, Scopus, and Cochrane Library databases were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data concerning patient demographics, validated patient reported outcome measures (PROMs) for pain relief, disability outcomes, complications, and reoperation rates were extracted and analyzed.
RESULTS
A total of 21 studies (18 retrospective and 3 prospective) were included in the quantitative analysis. A total of 826 patients (females = 75%) received coccygectomy (720 total and 106 partial) for refractory coccygodynia. Trauma was reported as the most common etiology of coccygodynia (56%; n = 375), followed by idiopathic causes (33%; n = 221). The pooled mean difference (MD) in pain scores from baseline on a 0-10 scale was 5.03 (95% confidence interval [CI]: 4.35 to 6.86) at a 6-12 month follow-up (FU); 5.02 (95% CI: 3.47 to 6.57) at > 12-36 months FU; and 5.41 (95% CI: 4.33 to 6.48) at > 36 months FU. The MCID threshold for pain relief was surpassed at each follow-up. Oswestry Disability Index scores significantly improved postoperatively, with a pooled MD from baseline of - 23.49 (95% CI: - 31.51 to - 15.46), surpassing the MCID threshold. The pooled incidence of complications following coccygectomy was 8% (95% CI: 5% to 12%), the most frequent of which were surgical site infections and wound dehiscence. The pooled incidence of reoperations was 3% (95% CI: 1% to 5%).
CONCLUSION
Coccygectomy represents a viable treatment option in patients with refractory coccygodynia.
Topics: Coccyx; Female; Humans; Low Back Pain; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 34694498
DOI: 10.1007/s00586-021-07041-6 -
Cancers Apr 2021Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly... (Review)
Review
Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.
PubMed: 33917001
DOI: 10.3390/cancers13081757