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1.
Front Immunol ; 15: 1359113, 2024.
Article in English | MEDLINE | ID: mdl-38571944

ABSTRACT

Acute Myeloid Leukemia (AML) is the prototype of cancer genomics as it was the first published cancer genome. Large-scale next generation/massively parallel sequencing efforts have identified recurrent alterations that inform prognosis and have guided the development of targeted therapies. Despite changes in the frontline and relapsed standard of care stemming from the success of small molecules targeting FLT3, IDH1/2, and apoptotic pathways, allogeneic stem cell transplantation (alloHSCT) and the resulting graft-versus-leukemia (GVL) effect remains the only curative path for most patients. Advances in conditioning regimens, graft-vs-host disease prophylaxis, anti-infective agents, and supportive care have made this modality feasible, reducing transplant related mortality even among patients with advanced age or medical comorbidities. As such, relapse has emerged now as the most common cause of transplant failure. Relapse may occur after alloHSCT because residual disease clones persist after transplant, and develop immune escape from GVL, or such clones may proliferate rapidly early after alloHSCT, and outpace donor immune reconstitution, leading to relapse before any GVL effect could set in. To address this issue, genomically informed therapies are increasingly being incorporated into pre-transplant conditioning, or as post-transplant maintenance or pre-emptive therapy in the setting of mixed/falling donor chimerism or persistent detectable measurable residual disease (MRD). There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Graft vs Leukemia Effect , Recurrence
2.
Clin Appl Thromb Hemost ; 30: 10760296241246004, 2024.
Article in English | MEDLINE | ID: mdl-38566600

ABSTRACT

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.


Subject(s)
Venous Thromboembolism , Venous Thrombosis , Humans , Anticoagulants/adverse effects , Venous Thromboembolism/drug therapy , International Normalized Ratio , Retrospective Studies , Prospective Studies , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Venous Thrombosis/drug therapy , Administration, Oral , Recurrence
3.
Open Heart ; 11(1)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38569669

ABSTRACT

INTRODUCTION: The primary concern for women who have experienced peripartum cardiomyopathy (PPCM) is the safety of a subsequent pregnancy (SSP). To maximie decision-making, facilitate effective patient counselling, and ultimately improve maternal and fetal outcomes as a whole, it is critical to comprehend the outcomes of SSP in women who have previously experienced PPCM. This study aimed to evaluate the outcomes of SSP in women with PPCM. METHODS: Three databases (PubMed, Scopus, and ScienceDirect) were used to identify relevant studies prior to 17 October 2023. A total of 662 studies were reviewed. Following the abstract and full-text screenings, 18 observational studies were included, out of which 2 were deemed suitable for inclusion in this meta-analysis. The quality assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: This study has a total of 487 SSPs. Although recovered left ventricular (LV) function before entering SSP has the potential to be a beneficial prognostic factor, recovered LV function still has a substantial risk of relapse. The mortality rate of PPCM in an SSP ranged from 0% to 55.5%. Persistent LV dysfunction was significantly associated with an increased mortality rate (OR 13.17; 95% CI 1.54 to 112.28; p=0.02) and lower LV ejection fraction (MD -12.88; 95% CI -21.67 to -4.09; p=0.004). Diastolic and right ventricular functions remained unchanged before SSP and at follow-up. The majority of the SSP was observed alongside hypertension, while pre-eclampsia emerged as the predominant hypertensive complication in most studies. CONCLUSION: SSP increases the risk of relapse and mortality in women with a previous history of PPCM. Persistent LV dysfunction prior to the SSP has a higher mortality risk compared with recovered LV function. SSP was also associated with the worsening of LV echocardiography parameters.


Subject(s)
Cardiomyopathies , Ventricular Dysfunction, Left , Pregnancy , Humans , Female , Peripartum Period , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy , Cardiomyopathies/complications , Ventricular Function, Left , Ventricular Dysfunction, Left/diagnostic imaging , Recurrence , Observational Studies as Topic
4.
J Psychiatry Neurosci ; 49(2): E135-E142, 2024.
Article in English | MEDLINE | ID: mdl-38569725

ABSTRACT

BACKGROUND: Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis. METHODS: We studied patients with psychosis within 2 years after the first psychotic event and healthy controls. We divided patients into 2 groups, namely those who did not experience relapse between disease onset and the magnetic resonance imaging (MRI) scan (no-relapse group) and those who did experience relapse between these 2 timings (relapse group). We analyzed 3003 functional connectivity estimates between 78 regions of interest (ROIs) derived from resting-state functional MRI data by adjusting for demographic and clinical confounding factors. RESULTS: We studied 85 patients, incuding 54 in the relapse group and 31 in the no-relapse group, along with 94 healthy controls. We observed significant differences in 47 functional connectivity estimates between the relapse and control groups after multiple comparison corrections, whereas no differences were found between the no-relapse and control groups. Most of these pathological signatures (64%) involved the thalamus. The Jonckheere-Terpstra test indicated that all 47 functional connectivity changes had a significant cross-group progression from controls to patients in the no-relapse group to patients in the relapse group. LIMITATIONS: Longitudinal studies are needed to further validate the involvement and pathological importance of the thalamus in relapse. CONCLUSION: We observed pathological differences in neuronal connectivity associated with relapse in early-stage psychosis, which are more specifically associated with the thalamus. Our study implies the importance of considering neurobiological mechanisms associated with relapse in the trajectory of psychotic disorders.


Subject(s)
Psychotic Disorders , Schizophrenia , Humans , Brain/diagnostic imaging , Magnetic Resonance Imaging , Neuroimaging , Chronic Disease , Recurrence
5.
Virol J ; 21(1): 79, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570803

ABSTRACT

BACKGROUND: No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). METHODS: A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. RESULTS: The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment. CONCLUSIONS: In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.


Subject(s)
Guanine/analogs & derivatives , Hematologic Neoplasms , Hepatitis B, Chronic , Humans , Tenofovir/therapeutic use , Antiviral Agents , Hepatitis B e Antigens , Viremia , Rituximab/therapeutic use , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/drug therapy , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/prevention & control , Hepatitis B virus , Adenine/therapeutic use , Hematologic Neoplasms/chemically induced , Hematologic Neoplasms/drug therapy , Treatment Outcome , Recurrence , Hepatitis B Surface Antigens
7.
J Immunother Cancer ; 12(4)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580329

ABSTRACT

BACKGROUND: Hematopoietic cell transplantation (HCT) is an effective treatment for pediatric patients with high-risk, refractory, or relapsed acute myeloid leukemia (AML). However, a large proportion of transplanted patients eventually die due to relapse. To improve overall survival, we propose a combined strategy based on cord blood (CB)-HCT with the application of AML-specific T cell receptor (TCR)-engineered T cell therapy derived from the same CB graft. METHODS: We produced CB-CD8+ T cells expressing a recombinant TCR (rTCR) against Wilms tumor 1 (WT1) while lacking endogenous TCR (eTCR) expression to avoid mispairing and competition. CRISPR-Cas9 multiplexing was used to target the constant region of the endogenous TCRα (TRAC) and TCRß (TRBC) chains. Next, an optimized method for lentiviral transduction was used to introduce recombinant WT1-TCR. The cytotoxic and migration capacity of the product was evaluated in coculture assays for both cell lines and primary pediatric AML blasts. RESULTS: The gene editing and transduction procedures achieved high efficiency, with up to 95% of cells lacking eTCR and over 70% of T cells expressing rWT1-TCR. WT1-TCR-engineered T cells lacking the expression of their eTCR (eTCR-/- WT1-TCR) showed increased cell surface expression of the rTCR and production of cytotoxic cytokines, such as granzyme A and B, perforin, interferon-γ (IFNγ), and tumor necrosis factor-α (TNFα), on antigen recognition when compared with WT1-TCR-engineered T cells still expressing their eTCR (eTCR+/+ WT1-TCR). CRISPR-Cas9 editing did not affect immunophenotypic characteristics or T cell activation and did not induce increased expression of inhibitory molecules. eTCR-/- WT1-TCR CD8+ CB-T cells showed effective migratory and killing capacity in cocultures with neoplastic cell lines and primary AML blasts, but did not show toxicity toward healthy cells. CONCLUSIONS: In summary, we show the feasibility of developing a potent CB-derived CD8+ T cell product targeting WT1, providing an option for post-transplant allogeneic immune cell therapy or as an off-the-shelf product, to prevent relapse and improve the clinical outcome of children with AML.


Subject(s)
Antineoplastic Agents , Leukemia, Myeloid, Acute , Humans , Child , CD8-Positive T-Lymphocytes , CRISPR-Cas Systems/genetics , Fetal Blood , Receptors, Antigen, T-Cell/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Cell Line, Tumor , Recurrence
8.
RMD Open ; 10(2)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38580345

ABSTRACT

OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV. METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively. RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Antibodies, Antineutrophil Cytoplasmic , Humans , Antibodies, Antineutrophil Cytoplasmic/genetics , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/genetics , Myeloblastin/genetics , Genotype , Recurrence
9.
BMJ Open ; 14(4): e086153, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38582538

ABSTRACT

INTRODUCTION: Epilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive models exist to determine who has a higher risk of recurrence to guide treatment. Emerging evidence suggests alterations in cognition, mood and brain connectivity exist in the population with UFS. Baseline evaluations of these factors following a UFS will enable the development of the first multimodal biomarker-based predictive model of seizure recurrence in adults with UFS. METHODS AND ANALYSIS: 200 patients and 75 matched healthy controls (aged 18-65) from the Kingston and Halifax First Seizure Clinics will undergo neuropsychological assessments, structural and functional MRI, and electroencephalography. Seizure recurrence will be assessed prospectively. Regular follow-ups will occur at 3, 6, 9 and 12 months to monitor recurrence. Comparisons will be made between patients with UFS and healthy control groups, as well as between patients with and without seizure recurrence at follow-up. A multimodal machine-learning model will be trained to predict seizure recurrence at 12 months. ETHICS AND DISSEMINATION: This study was approved by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board at Queen's University (DMED-2681-22) and the Nova Scotia Research Ethics Board (1028519). It is supported by the Canadian Institutes of Health Research (PJT-183906). Findings will be presented at national and international conferences, published in peer-reviewed journals and presented to the public via patient support organisation newsletters and talks. TRIAL REGISTRATION NUMBER: NCT05724719.


Subject(s)
Epilepsy , Seizures , Adult , Humans , Prospective Studies , Recurrence , Seizures/epidemiology , Epilepsy/epidemiology , Electroencephalography , Nova Scotia , Multicenter Studies as Topic
10.
Europace ; 26(4)2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38584395

ABSTRACT

AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7 ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8 min, and fluoroscopy time was 13.1 ± 7.6 min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Pulmonary Veins/surgery , Treatment Outcome , Prospective Studies , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Catheters , Catheter Ablation/adverse effects , Catheter Ablation/methods , Magnetic Phenomena , Recurrence
11.
Front Endocrinol (Lausanne) ; 15: 1364316, 2024.
Article in English | MEDLINE | ID: mdl-38590823

ABSTRACT

Background: Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC). Objective: To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation. Method: Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice. Results: Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse. Conclusion: For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.


Subject(s)
Bone Marrow , Leukemia , Female , Humans , Animals , Mice , Transplantation, Heterologous , Mice, Nude , Emaciation , Mice, Inbred BALB C , Cryopreservation , Recurrence
12.
Cancer Med ; 13(7): e7182, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38591109

ABSTRACT

BACKGROUND: Acute myeloid leukemia (AML) is characterized by clonal heterogeneity, leading to frequent relapses and drug resistance despite intensive clinical therapy. Although AML's clonal architecture has been addressed in many studies, practical monitoring of dynamic changes in those subclones during relapse and treatment is still understudied. METHOD: Fifteen longitudinal bone marrow (BM) samples were collected from three relapsed and refractory (R/R) AML patients. Using droplet digital polymerase chain reaction (ddPCR), the frequencies of patient's leukemic variants were assessed in seven cell populations that were isolated from each BM sample based on cellular phenotypes. By quantifying mutant clones at the diagnosis, remission, and relapse stages, the distribution of AML subclones was sequentially monitored. RESULTS: Minimal residual (MR) leukemic subclones exhibit heterogeneous distribution among BM cell populations, including mature leukocyte populations. During AML progression, these subclones undergo active phenotypic transitions and repopulate into distinct cell population regardless of normal hematopoiesis hierarchic order. Of these, MR subclones in progenitor populations of patient BM predominantly carry MR leukemic properties, leading to more robust expansion and stubborn persistence than those in mature populations. Moreover, a minor subset of MR leukemic subclones could be sustained at an extremely low frequency without clonal expansion during relapse. CONCLUSIONS: In this study, we observed treatment persistent MR leukemic subclones and their phenotypic changes during the treatment process of R/R AML patients. This underscores the importance of preemptive inhibition of clonal promiscuity in R/R AML, proposing a practical method for monitoring AML MR subclones.


Subject(s)
Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Clone Cells , Chronic Disease , Recurrence
13.
J Gastrointest Surg ; 28(4): 507-512, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38583903

ABSTRACT

BACKGROUND: The risk of recurrence is an important consideration when deciding to treat patients medically or with elective colectomy after recovery from diverticulitis. It is unclear whether age is associated with recurrence. This study aimed to examine the relationship between age and the risk of recurrent diverticulitis while considering important epidemiologic factors, such as birth decade. METHODS: The Utah Population Database was used to identify individuals with incident severe diverticulitis, defined as requiring an emergency department visit or hospitalization, between 1998 and 2018. This study measured the relationship between age and recurrent severe diverticulitis after adjusting for birth decade and other important variables, such as sex, urban/rural status, complicated diverticulitis, and body mass index using a Cox proportional hazards model. RESULTS: The cohort included 8606 individuals with a median age of 61 years at index diverticulitis diagnosis. After adjustment, among individuals born in the same birth decade, increasing age at diverticulitis onset was associated with an increased risk of recurrent diverticulitis (hazard ratio [HR] for 10 years, 1.8; 95% CI, 1.5-2.1). Among individuals with the same age of onset, those born in a more recent birth decade were also at greater risk of recurrent diverticulitis (HR, 1.9; 95% CI, 1.6-2.3). CONCLUSION: Among individuals with an index episode of severe diverticulitis, recurrence was associated with increasing age and more recent birth decade. Clinicians may wish to employ age-specific strategies when counseling patients regarding treatment options after a diverticulitis diagnosis.


Subject(s)
Diverticulitis, Colonic , Diverticulitis , Humans , Middle Aged , Child , Diverticulitis, Colonic/epidemiology , Diverticulitis, Colonic/surgery , Diverticulitis, Colonic/complications , Retrospective Studies , Diverticulitis/complications , Hospitalization , Colectomy/adverse effects , Recurrence
15.
Iran J Med Sci ; 49(3): 156-166, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38584650

ABSTRACT

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.


Subject(s)
Carcinoma , Papillomavirus Infections , Paranasal Sinus Neoplasms , Humans , Vascular Endothelial Growth Factor A , bcl-2-Associated X Protein , Human Papillomavirus Viruses , Prognosis , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Papillomaviridae , Neoplasm Recurrence, Local/complications , Carcinoma/diagnosis , Carcinoma/pathology , Paranasal Sinus Neoplasms/diagnosis , Paranasal Sinus Neoplasms/pathology , ErbB Receptors , Recurrence , Biomarkers
16.
World J Urol ; 42(1): 221, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587648

ABSTRACT

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.


Subject(s)
Fosfomycin , Urinary Tract Infections , Humans , Anti-Bacterial Agents/therapeutic use , Fosfomycin/therapeutic use , Nitrofurantoin , Trimethoprim, Sulfamethoxazole Drug Combination , Network Meta-Analysis , Urinary Tract Infections/drug therapy , Ciprofloxacin/therapeutic use , Recurrence
17.
BMC Infect Dis ; 24(1): 364, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38556907

ABSTRACT

BACKGROUND: The emergence of Drug Resistant Tuberculosis (DR-TB) is one of the main public health and economic problems facing the world today. DR-TB affects mostly those in economically productive years and prevents them from being part of the workforce needed for economic growth. The aim of this study was to determine the Clinical Profile and Outcomes of DR-TB in Central Province of Zambia. METHODS: This was a retrospective cross sectional study that involved a review of records of patients with confirmed DR-TB who were managed at Kabwe Central Hospital's Multi-Drug Resistant TB (MDR-TB) Ward from the year 2017 to 2021. 183 patients were managed during this period and all were recruited in the study. Data was collected from DR-TB registers and patient files and then entered in SPSS version 22 where all statistical analyses were performed. RESULTS: The study revealed that the prevalence of DR-TB among registered TB patients in Central Province was 1.4%. Majority of those affected were adults between the ages of 26 and 45 years (63.9%). The study also found that more than half of the patients were from Kabwe District (60.7%). Other districts with significant number of cases included Kapiri Mposhi 19 (10.4%), Chibombo 12 (6.6%), Chisamba 10 (5.5%), Mumbwa 7 (3.8%) and Mkushi 7 (3.8%). Furthermore, the analysis established that most of the patients had RR-TB (89.6%). 9.3% had MDR-TB, 0.5% had IR-TB and 0.5% had XDR-TB. RR-TB was present in 93.8% of new cases and 88.9% of relapse cases. MDR-TB was present in 6.2% of new cases and 10% of relapse cases. With regard to outcomes of DR-TB, the investigation revealed that 16.9% of the patients had been declared cured, 45.9% had completed treatment, 6% were lost to follow up and 21.3% had died. Risk factors for mortality on multivariate analysis included age 36-45 years (adjusted odds ratio [aOR] 0.253, 95% CI [0.70-0.908] p = 0.035) and male gender (aOR 0.261, 95% CI [0.107-0.638] p = 0.003). CONCLUSION: The research has shown beyond doubt that the burden of DR-TB in Central Province is high. The study recommends putting measures in place that will help improve surveillance, early detection, early initiation of treatment and proper follow up of patients.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Adult , Humans , Male , Middle Aged , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Cross-Sectional Studies , Prevalence , Recurrence , Retrospective Studies , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Zambia/epidemiology , Female
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 269-274, 2024 Mar 15.
Article in Chinese | MEDLINE | ID: mdl-38557379

ABSTRACT

OBJECTIVES: To observe the correlation between growth impairment induced by long-term oral glucocorticoids (GC) therapy and the ratio of FGF23/Klotho in children with primary nephrotic syndrome (PNS). METHODS: A prospective study was conducted on 56 children with GC-sensitive PNS who had discontinued GC therapy for more than 3 months and revisited the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine between June 2022 and December 2022. After monitoring qualitative and quantitative urine protein levels upon admission, the children with proteinuria relapse were treated with GC (GC group; n=29), while those without relapse did not receive GC treatment (non-GC group; n=27). In addition, 29 healthy children aged 3 to prepuberty were selected as the control group. Height, bone age, growth rate, and the FGF23/Klotho ratio were compared among the groups. The correlations of the FGF23/Klotho ratio with height, bone age, and growth rate were analyzed. RESULTS: The FGF23/Klotho ratio in the GC group was significantly higher than that in the non-GC group after 1 month of GC therapy (P<0.05), and the height and bone age growth rates within 6 months were lower than those in the non-GC group (P<0.05). Correlation analysis showed significant negative correlations between the FGF23/Klotho ratio after 1 month of treatment and the growth rates of height and bone age within 6 months in children with PNS (r=-0.356 and -0.436, respectively; P<0.05). CONCLUSIONS: The disturbance in FGF23/Klotho homeostasis is one of the mechanisms underlying the growth impairment caused by long-term oral GC therapy.


Subject(s)
Glucocorticoids , Glucuronidase , Humans , Child , Glucocorticoids/adverse effects , Prospective Studies , Fibroblast Growth Factors , Recurrence
19.
Hematol Oncol ; 42(3): e3265, 2024 May.
Article in English | MEDLINE | ID: mdl-38564328

ABSTRACT

The next-generation sequencing technologies application discovers novel genetic alterations frequently in pediatric acute lymphoblastic leukemia (ALL). RAS signaling pathway mutations at the time of relapse ALL frequently appear as small subclones at the time of onset, which are considered as the drivers in ALL relapse. Whether subclones alterations in the RAS signaling pathway should be considered for risk group stratification of ALL treatment is not decided yet. In this work, we investigate the RAS signaling pathway mutation spectrum and the related prognosis in pediatric ALL. We employed an NGS panel comprising 220 genes. NGS results were collected from 202 pediatric ALL patients. 155 patients (76.7%) harbored at least one mutation. The incidences of RAS signaling pathway mutations are different significantly between T-ALL and B-ALL. In B-ALL, the RAS pathway is mostly involved, and NRAS (17.6%), KRAS (22.7%), and PTPN11 (7.7%) were the three most frequently mutated genes. Co-occurring mutations of CREBBP and NRAS, FLT3, or PTPN11 (p = 0.002, p = 0.009, and p = 0.003, respectively) were found in this cohort. The 3-year RFS rates for the RAS signaling pathway mutation-positive and negative cases was 76.5 % versus 89.7 % (p = 0.012). Four cases relapsed in the lately 3 years were RAS signaling pathway mutation-positive. RAS signaling pathway mutation is an important biomarker for poorer relapse-free survival in pediatric B-ALL patients despite good early MRD levels.


Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Mutation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Signal Transduction , Prognosis , Recurrence
20.
Eur Rev Med Pharmacol Sci ; 28(6): 2161-2167, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38567578

ABSTRACT

OBJECTIVE: The purpose of this study is to evaluate the effect of sarcopenia on overall survival and local relapse in head and neck cancer patients undergoing surgical excision. PATIENTS AND METHODS: This retrospective study includes head and neck cancer patients primarily treated with surgical excision in a tertiary care center. Patients were included if they had undergone an abdominal region Computer Tomography scan at least 45 days before the surgical excision. Hospital records were collected, and data analysis included patient demographics, comorbidities, tumor staging, surgical details, adjuvant therapy details, treatment complications, death records, and last follow-up appointment details. RESULTS: In this retrospective study, 138 head and neck cancer patients were included, with 69.6% males and 30.4% females. The mean age was 60.2±12.3 years, and the average follow-up time was 54.3±16.3 months. Sarcopenia was present in 48.6% of patients and absent in 51.4%. Sarcopenic patients had a significantly lower mean age compared to non-sarcopenic patients (p<0.05). The proportion of larynx cancer was significantly lower in the sarcopenia group compared to the non-sarcopenia group (p<0.05). According to the American Joint Committee on Cancer (AJCC) staging, stage IV was significantly higher in the sarcopenia group (p<0.05). Local relapse was significantly higher in the sarcopenia group (p<0.05). CONCLUSIONS: The findings of this study emphasize the importance of sarcopenia evaluation in determining prognosis and identifying patients who may benefit from specialized and intensive nutritional programs. Sarcopenia harms overall survival and local relapse in head and neck cancer patients.


Subject(s)
Head and Neck Neoplasms , Sarcopenia , Male , Female , Humans , Middle Aged , Aged , Sarcopenia/pathology , Retrospective Studies , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/complications , Prognosis , Recurrence
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