OBJECTIVE: Hematological malignancies (HMs) are a group of neoplasms with hematopoietic origin, currently divided into leukemias, lymphomas and multiple myeloma (MM). Although the advances in the management of HMs, the rate of drug resistance, relapse and refractory disease has been increasing, requiring new therapeutic strategies. In this review, we aim to summarize metformin\'s antitumoral mechanisms of action and present the latest studies of metformin action in HMs, including in resistant ones.
METHODS: For this review of literature, studies published between 1996 and 2023 from PubMed and clinical trials submitted to clinicaltrials.gov were considered.
UNASSIGNED: Throughout this review we demonstrated the capacity of metformin to act as an anti-HMs drug, being able to re-sensitize HMs to classical anti-HMs agents and to overcome relapse and refractory HMs, as shown in vitro and in vivo studies. Associated with the potential anti-HM effect of metformin, some clinical trials are in progress, including in the view of reducing resistance and recurrence rate of HMs, which requires further exploration. The relationship among HMs cancer stem cells (HMs CSCs), drug resistance, cancer recurrence, and the effect of metformin in inhibiting CSCs were also discussed, despite this field needing more attention.
CONCLUSIONS: In summary, metformin is a promising anti-HMs drug that can enhance patients\' survival and prognosis through its action in the improvement of HMs response.

BACKGROUND: Bipolar disorder (BD) is a chronic and recurrent illness characterized by manic, mixed or depressive episodes, alternated with periods of euthymia. Several prognostic factors are associated with higher rates of relapse, which is crucial for the identification of high-risk individuals. This study aimed at systematically reviewing the existing literature regarding the impact of sociodemographic, clinical and environmental factors, in clinical relapses, recurrences and hospitalizations due to mood episodes in BD.
METHODS: A systematic search of electronic databases (PubMed, Cochrane library and Web of Science) was conducted to integrate current evidence about the impact of specific risk factors in these outcomes.
RESULTS: Fifty-eight articles met the inclusion criteria. Studies were grouped by the type of factors assessed. Family and personal psychiatric history, more severe previous episodes, earlier age of onset, and history of rapid cycling are associated with clinical relapses, along with lower global functioning and cognitive impairments. Unemployment, low educational status, poorer social adjustment and life events are also associated with higher frequency of episodes, and cannabis with a higher likelihood for rehospitalization.
CONCLUSIONS: Small sample sizes, absence of randomized clinical trials, diverse follow-up periods, lack of control for some confounding factors, heterogeneous study designs and diverse clinical outcomes.
CONCLUSIONS: Although current evidence remains controversial, several factors have been associated with an impaired prognosis, which might allow clinicians to identify patients at higher risk for adverse clinical outcomes and find modifiable factors. Further research is needed to elucidate the impact of each risk factor in the mentioned outcomes.

Approximately one third of children with rhabdomyosarcoma relapse or have refractory disease. Treatment approaches include a combination of systemic therapies and local therapies, directed at tumour site(s). This review was conducted to evaluate the effectiveness and safety of the combination of surgery and brachytherapy as local therapy for treating children and young people with relapsed/refractory rhabdomyosarcoma. This review identified studies based on a previous systematic review looking at the treatments for children and young people under 18 years old with relapsed/refractory rhabdomyosarcoma. Studies conducted after 2000 were included. Survival outcomes, relapse rates, adverse events and functional outcomes were extracted. From 16,965 records identified in the baseline systematic review, 205 included the words \'AMORE\' or \'brachytherapy\', and were screened for eligibility in this substudy. Thirteen studies met the inclusion criteria for Local-REFoRMS, including over 55 relapsed and refractory rhabdomyosarcoma patients. Most studies were retrospective cohort studies conducted within Europe. Most patients had embryonal disease within the head and neck or bladder/prostate regions, and received local therapy for first relapse. Approximately one quarter of patients relapsed following surgery and brachytherapy, with local relapses occurring more than metastatic relapse. Adverse events and functional outcomes were infrequently reported, but related to the site of surgery and brachytherapy. Study quality was limited by inconsistent reporting and potential selection bias. Outcomes following surgery and brachytherapy for a selected group of relapsed and refractory rhabdomyosarcoma show reasonable benefits, but reporting was often unclear and based on small sample sizes.

OBJECTIVE: Despite high rates of relapse after treatment for drug use, to our knowledge there is no systematic literature identifying psychological factors that predict risk of relapse to drug use (excluding alcohol or tobacco). Our aim was to identify psychological factors that predict risk of relapse to drug use after enrollment in drug use treatment. The identification of such factors can support treatment planning and relapse prevention.
METHODS: We searched for peer-reviewed articles published between 2000 and 2023 in PsycINFO, PsycArticles, Web of Science, and PubMed. The inclusion criteria were: peer-reviewed publications, quantitative studies, in English, adult samples, with a prospective design, and analyses of minimum one psychological factor as predictor of relapse to drug use. All authors were involved in abstract and full-text screening, and in assessing risk of bias. The findings are presented in a narrative synthesis and tables are organized by type of drug.
RESULTS: Of 2226 publications initially identified, 45 were eligible. Twenty-three focused on predicting relapse to stimulants, 15 to opioids, and 7 to unspecified drugs. Substance use at baseline was an important factor predicting risk of relapse to opioids, and possibly stimulants. There was an indication that craving and attention problems potentially predict relapse to use of some drugs. Mental health factors (e.g., psychiatric diagnosis) did not predict relapse. Several psychological factors (e.g., cognition, emotion, personality, motivation) were scarcely examined. Over half of the studies had moderate to high risk of bias.
CONCLUSIONS: Based on the 45 studies, few psychological factors predicted risk of relapse to drug use. Higher comparability between studies and more rigorous methodology are necessary in order to derive more precise recommendations that inform and improve clinical practice.
UNASSIGNED: PROSPERO, CRD42020182839.

Despite therapeutic advances for acute promyelocytic leukemia (APL) with the emergence of all-trans retinoic acid, arsenic trioxide, and gemtuzumab-ozogamycin, approximately 10% of patients still experience disease relapse, typically occurring within 24 to 36 months following completion of front-line treatment. Traditionally, both allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) have been considered reasonable treatment options for relapsed APL; however, no randomized controlled studies have been conducted comparing allo-HCT and auto-HCT in patients with relapsed APL. We performed a systematic review/meta-analysis to assess the totality of evidence pertaining to allo-HCT or auto-HCT in relapsed APL. Our search identified 1158 references, of which 23 met our inclusion criteria. While acknowledging the limitations of comparing these 2 treatment modalities indirectly, based on results from separate meta-analyses, it appears that pooled rates of event-free survival (71% versus 54%), progression-free survival (63% versus 43%), and overall survival (82% versus 58%) are higher after auto-HCT. This difference can be explained in part by the higher risk of pooled nonrelapse mortality (NRM) in patients undergoing allo-HCT (29% versus 5%), owing to inherent risks associated with this modality. In the absence of a randomized prospective clinical trial comparing allo-HCT and auto-HCT, our results show that both modalities are acceptable in patients with relapsed APL. The higher pooled NRM rate with allo-HCT is an important consideration when choosing this option. Additionally, the comparable pooled relapse rate for auto-HCT and allo-HCT (24% versus 23%) provides a rationale for evaluating post-HCT consolidative strategies to mitigate this risk.

This systematic review examines studies published between 2003, the initial invasion of Iraq, and 2018 related to the long-term treatment outcomes for Veterans of Iraq and Afghanistan suffering from combat-related posttraumatic stress disorder (PTSD). More specifically this review attempts to estimate the rate at which Veterans experience the return of symptoms after completing treatment. The review was conducted by the authors in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The literature search identified eight eligible studies, which met the predefined inclusion criteria. Of the included studies a majority were deemed to be at a high risk of attrition bias. In addition, few studies comprehensively reported relevant relapse or recurrence related outcome statistics. The implications of the available evidence base on long-term treatment outcomes are discussed. Recommendations for future studies on relapse and recurrence of PTSD symptoms among Veterans of Iraq and Afghanistan are also presented.

Gastrointestinal stromal tumors (GISTs) represent a rare form of gastrointestinal neoplasm. This report details a medical case involving a 44-year-old woman who underwent bilateral pheochromocytoma resection, GIST gastrectomy, and laparoscopic adrenalectomy with intestinal resection. Despite an initially positive response to oral imatinib, treatment was delayed due to economic constraints. This delay resulted in a critical event marked by abdominal GIST metastasis to the abdominal wall, subsequent rupture leading to hemoperitoneum, and emergency surgery. Following an adequate postsurgical recovery, she was successfully discharged prior to medication adjustments.

UNASSIGNED: Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to quantify the proportion of relapses observed at and beyond 6-months using the Infectious Diseases Data Observatory (IDDO) systematic review (SR) database.
UNASSIGNED: Studies in the IDDO SR database (1983-2021; 160 studies) were eligible for inclusion if follow-up was at least 6-months, relapse was clearly reported, and patients with HIV coinfections were excluded. Meta-analysis of single proportion was undertaken and the estimates were reported with 95% confidence intervals (CI).
UNASSIGNED: Overall, 131 studies enrolling 27,687 patients were included; 1193 patients relapsed. In the Indian sub-continent (ISC), relapse estimates at 6-months was 4.5% [95% CI: 2.6%-7.5%; I2 = 66.2%] following single dose liposomal amphotericin B (L-AmB) and 1.5% [95% CI: 0.7%-3.3%; I2 = 0%] for L-AmB in a combination therapy. In East Africa (EA), corresponding estimates were 3.8% [95% CI: 1.3%-10.9%; I2 = 75.8%] following pentavalent antimony (PA), and 13.0% [95% CI: 4.3%-33.6%; I2 = 0%] for PA + paromomycin. From 21 studies with follow-up longer than 6-months, 0.6% [95% CI: 0.2%-1.8%; I2 = 0%] of patients relapsed after 6-months and estimated 27.6% [95% CI: 11.2%-53.4%; I2 = 12%] of relapses would have been missed by a 6-month follow-up.
UNASSIGNED: The estimated relapse proportion ranged from 0.5% to 4.5% in ISC and 3.8%-13.0% in EA with the currently recommended drugs. Over one-quarter of relapses would be missed with 6-months follow-up suggesting a longer follow-up may be warranted.
UNASSIGNED: Wellcome Trust (ref: 208378/Z/17/Z).

UNASSIGNED: Treatment for rifampicin-resistant tuberculosis (RR-TB) has been shortened to 12 months or less, with duration depending on the regimen used and treatment response. Treatment shortening has the potential to increase the risk of relapse, with a new episode of RR-TB after cure or completion. The proportion of relapses after standardized all-oral short (12 months or less) RR-TB regimens has not yet been systematically reviewed, which is the main objective of this review.
UNASSIGNED: This is a systematic review and meta-analysis. PubMed, Web of Science and Google scholar databases were systematically investigated to identify studies published between January 2018 and November 2023. Characteristics of studies, demographic data, baseline clinical condition, resistance profile, and definitions used for relapse, failure, and end-of-treatment outcomes are summarized in tables and graphs. Pooled proportions are estimated for relapse.
UNASSIGNED: A total of ten studies were included in this review and meta-analysis, representing 1792 participants. Seven studies were clinical trials and two were cohorts. Five studies investigated all-oral six-month regimens composed of bedaquiline, pretomanid, and linezolid (BPaL). The remaining studies assessed other standardized all-oral short regimens, with treatment duration between 6 and 12 months. Post-treatment follow-up (PTFU) duration ranged from 6 to 30 months. The pooled proportion estimate of relapse was 2·0% (95 % CI, 1·0-3·0%) for all and BPaL-based regimens. Treatment extension due to poor treatment response was poorly documented.
UNASSIGNED: This review showed that the proportion of relapse in RR-TB patients treated with standardized short all-oral regimens was low. The low relapse proportion is similar to what was achieved for drug-susceptible Tuberculosis patients treated with first-line rifampicin-containing regimens. However, most data came from trial settings, and in some studies the post-treatment follow-up was short. Studies of large programmatic cohorts with longer post-treatment follow-up periods are needed to confirm the low relapse rate shown in the clinical trials.

UNASSIGNED: Fingolimod and interferons are used in the relapse form of multiple sclerosis (MS). The goal of this systematic review and meta-analysis was to evaluate the efficacy of fingolimod versus interferon in patients with MS. The systematic search was done in PubMed, Scopus, Embase, Web of Science, and Google Scholar.
UNASSIGNED: The references of included studies as well as conference abstracts were searched up to July 2021. The literature search revealed 8211 articles, and after deleting duplicates 5594 remained. For the meta-analysis, four studies were included. The standardized mean difference (SMD) of the Expanded Disability Status Scale (EDSS) after treatment (interferon vs fingolimod) was -0.06 (95% CI: -0.28, 0.17) (I2 = 80.2%, P = 0.002).
UNASSIGNED: The SMD of the annual relapse rate (ARR) after treatment (interferon - fingolimod) was -0.08 (95% CI: -0.53, 0.36) (I2 = 95.5%, P < 0.001). The SMD of the ARR after treatment and before treatment in the interferon group was - 1.45, (95% CI: -1.55, -1.36) (I2 = 0, P = 0.3). The SMD of ARR after treatment and before treatment in the fingolimod group was - 1.3, (95% CI: -1.94, -0.65) (I2 = 97.4%, P < 0.001). Conclusions: The results of this systematic review show that efficacy of interferon and fingolimod in controlling relapse rate and disability is similar.