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World Journal of Gastroenterology May 2024The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of...
BACKGROUND
The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated.
AIM
To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC.
METHODS
We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.
RESULTS
The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs).
CONCLUSION
The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Fluorouracil; Infusions, Intra-Arterial; Leucovorin; Aged; Adult; Hepatic Artery; Organoplatinum Compounds; Treatment Outcome; Molecular Targeted Therapy; Progression-Free Survival; Retrospective Studies; Immunotherapy; Combined Modality Therapy
PubMed: 38813052
DOI: 10.3748/wjg.v30.i17.2321 -
Arquivos de Neuro-psiquiatria May 2024Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity...
BACKGROUND
Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations.
OBJECTIVE
To describe the diagnostic features and response to treatment in our cohort of WD patients.
METHODS
This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, genotyping, and response to treatment.
RESULTS
Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs ( = 0.2). Nine patients underwent liver transplantation and 82 died.
CONCLUSION
Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include genotyping and therapeutic alternatives in clinical practice.
Topics: Humans; Hepatolenticular Degeneration; Retrospective Studies; Female; Male; Adolescent; Child; Adult; Copper-Transporting ATPases; Young Adult; Penicillamine; Treatment Outcome; Middle Aged; Adenosine Triphosphatases; Mutation; Genotype; Magnetic Resonance Imaging; Chelating Agents; Cation Transport Proteins; Copper
PubMed: 38811021
DOI: 10.1055/s-0044-1786855 -
Journal of Osteopathic Medicine May 2024This national needs assessment study explores the knowledge, attitude, beliefs, and practices (KABP) gaps related to vasomotor symptoms (VMS) associated with menopause...
CONTEXT
This national needs assessment study explores the knowledge, attitude, beliefs, and practices (KABP) gaps related to vasomotor symptoms (VMS) associated with menopause among primary care and OB/GYN clinicians. VMS significantly impacts healthcare costs, workplace productivity, and patient psychosocial health, but a notable disconnect exists between healthcare providers and patients, with provider reticence and knowledge gaps playing a contributing role.
OBJECTIVES
This study aims to identify and propose optimal educational strategies to address these barriers, with attention to health disparities affecting women of color.
METHODS
Methods employed include a multimodal approach of literature review, expert opinion, qualitative interviews, surveys, focus groups, and case studies, ensuring diverse clinician input. Data collection involved in-depth clinician interviews, a nationally disseminated clinician survey, and focus groups.
RESULTS
Results indicate a critical deficiency in healthcare providers' understanding and management of VMS, especially among OB/GYN residents, with 75 % showing limited knowledge. The study also highlights the disproportionate impact of knowledge gaps on women of color, emphasizing the need for a culturally informed approach in medical training and practice. There's a notable discrepancy between clinicians' current and desired abilities in managing VMS, indicating a need for ongoing professional development. Significant variability in approaches to diagnosing and treating VMS, as well as substantial knowledge gaps about treatment options, underscore the need for evidence-based protocols.
CONCLUSIONS
Although VMS are a normal aspect of aging, they can significantly disrupt quality of life for many women, necessitating intervention. Beyond the immediate discomfort, VMS can impact quality of life and trigger insomnia and mood disturbances. This study exposes both new and previously recognized gaps in healthcare providers' knowledge and management skills concerning VMS treatment options, particularly regarding hormonal and nonhormonal therapies. Furthermore, our findings highlight the need for a deeper understanding of how VMS uniquely impacts women of diverse backgrounds. Research, including the Study of Women's Health Across the Nation (SWAN), suggests that the experience and severity of VMS may be influenced by socioeconomic status, race/ethnicity, body mass index (BMI), and smoking status. However, the complex interplay of these factors and their relative contributions remain unclear. Further investigation is crucial to facilitate equitable access to effective treatment for all women. To bridge these gaps, improved education starting as early as residency is essential. This education should address common misconceptions about VMS and its management. Healthcare providers must enhance their competence in discussing the broad spectrum of VMS impacts and employ effective communication strategies to ensure that patients are well-informed about their symptoms and available treatment options.
PubMed: 38809719
DOI: 10.1515/jom-2024-0011 -
Pulmonary Circulation Apr 2024Pulmonary hypertension in sickle cell disease (SCD) is a complex phenomenon resulting from multiple overlapping etiologies, including pulmonary vasoconstriction in the...
Pulmonary hypertension in sickle cell disease (SCD) is a complex phenomenon resulting from multiple overlapping etiologies, including pulmonary vasoconstriction in the setting of chronic hemolytic anemia, diastolic dysfunction, and chronic thromboembolic disease. The presence of pulmonary hypertension of any cause in SCD confers a significant increase in mortality risk. Evidence to guide the management of patients with sickle cell disease and chronic thromboembolic pulmonary hypertension (CTEPH) is scant and largely the realm of case reports and small case series. Centered on a discussion of a complex young patient with hemoglobin hemoglobin SC who ultimately underwent treatment with pulmonary thromboendarterectomy, we review the available literature to guide management and discuss and overview of treatment of CTEPH in SCD, considering the unique considerations and challenges facing patients suffering from this multisystem disease.
PubMed: 38803827
DOI: 10.1002/pul2.12362 -
Drug Design, Development and Therapy 2024Remimazolam tosilate is a novel ultrafast-acting benzodiazepine that has a rapid emergence even after continuous infusion when using flumazenil. So far, relatively few... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Clinical Trial
Comparison of Remimazolam Tosilate and Propofol Sedation on the Early Postoperative Quality of Recovery in Patients Undergoing Day Surgery: A Prospective Randomized Controlled Trial.
PURPOSE
Remimazolam tosilate is a novel ultrafast-acting benzodiazepine that has a rapid emergence even after continuous infusion when using flumazenil. So far, relatively few articles are still focusing on the quality of recovery after general anesthesia with remimazolam, especially in day surgery. This study aimed to compare the early postoperative quality of recovery of remimazolam tosilate with flumazenil and propofol in patients undergoing day surgery.
PATIENTS AND METHODS
137 patients scheduled for day surgery were randomly divided into the remimazolam tosilate or propofol group. The primary endpoint was the incidence of overall recovery assessed with the early postoperative quality of recovery scale (PostopQRS) on postoperative day 1 (POD 1). The Richmond Agitation-Sedation Scale (RASS) scores in the post-anesthesia care unit (PACU), extubation time, postoperative recovery profiles, and perioperative data were documented. Any adverse events were recorded.
RESULTS
The incidence of overall recovery on POD1 was 47.7% in the remimazolam tosilate group and 65.1% in the propofol group (odds ratio, 0.52; 95% confidence interval (CI) 0.26 to 1.06; P = 0.072). In general, the overall recovery of the PostopQRS increased over time, and its interaction between time and group was significant (P = 0.003). Among the five dimensions of PostopQRS, there exist statistical differences between groups including emotional state and cognitive recovery. Upon arrival at the PACU, the remimazolam group was more sedated and took longer to recover to a RASS score similar to propofol. The frequency of application of vasoactive drugs during anesthesia was similar in both groups (P = 0.119). Despite rapid emergence with remimazolam after flumazenil reversal, re-sedation (10.8%) or somnolence (60%) in the PACU was observed, and the length of PACU stay in patients treated with remimazolam tosilate was longer than that of the propofol (35 min vs 30 min, P<0.001).
CONCLUSION
General anesthesia with remimazolam tosilate in conjunction with flumazenil reversal permits rapid recovery of consciousness in day surgery, but there was a notable occurrence of re-sedation or somnolence observed in PACU.
Topics: Humans; Propofol; Female; Male; Prospective Studies; Middle Aged; Benzodiazepines; Hypnotics and Sedatives; Adult; Ambulatory Surgical Procedures; Anesthesia Recovery Period; Aged; Flumazenil
PubMed: 38803562
DOI: 10.2147/DDDT.S456675 -
Scientific Reports May 2024The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with...
The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with digestive tract, and 36 with breast carcinomas (BC) in advanced stages with poor prognostic characteristics. Patients with colorectal, and pancreas adenocarcinoma received oxaliplatin, irinotecan, FUra, FA (Folfirinox), and patients with squamous cell carcinoma of the esophagus had paclitaxel, carboplatin, FUra, FA (TCbF). Patients with BC received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) followed by TCbF or TCbF only, and patients who overexpressed HER2 received TCbF plus trastuzumab and pertuzumab. PN (1000-3000 mg/day iv) preceded each administration of FUra and FA. 47 patients (94%) responded, including 16 (32%) with CR. Median tumor reduction was 93%. Median event-free survival (EFS) was 37.7 months. The 25 patients with tumor shrinkage ≥ 91% had EFS of 52% from 42 months onwards. Unexpected toxicity did not occur. PN enhances potency of chemotherapy regimens comprising FUra and FA.
Topics: Humans; Fluorouracil; Leucovorin; Pyridoxine; Female; Middle Aged; Aged; Male; Antineoplastic Combined Chemotherapy Protocols; Adult; Breast Neoplasms; Neoplasm Staging; Treatment Outcome
PubMed: 38802419
DOI: 10.1038/s41598-024-62860-z -
Cureus Apr 2024Central and autonomic nervous system signs of organophosphate poisoning (OP), such as altered consciousness, noticeable lacrimation, and salivation, can be influenced by...
Central and autonomic nervous system signs of organophosphate poisoning (OP), such as altered consciousness, noticeable lacrimation, and salivation, can be influenced by medications used in intensive care settings, such as atropine and pralidoxime methyl (PAM). Because of this, there are no established methods for assessing the duration of OP while receiving antidotal treatment. In the present case, we used the Neurological Pupil Index (NPi) to evaluate the duration of OP in an 82-year-old woman who attempted suicide by ingesting up to 100 mL of fenitrothion. Until hospitalization day (HD) 20, discontinuation of atropine led to the recurrence of altered consciousness, while its reinstatement resulted in improvement; this made it difficult to assess the prolongation of OP based on signs and symptoms. Until HD 20, the NPi remained at 0/0, and subsequently, it increased. Additionally, even after discontinuing atropine, consciousness, tearing, and salivation did not worsen, indicating recovery from OP. On HD 26, serum acetylcholinesterase (AChE) levels were elevated above the measurable level for the first time, following an increase in the NPi. In this case, assessing the persistence of OP based on signs was challenging because these signs improved with atropine and PAM treatment. The improvement in NPi levels coincided with an improvement in poisoning, suggesting that NPi is useful for evaluating the duration of OP. NPi is noninvasive and sensitive compared to AChE, which is used to gauge the persistence of OP and could be used to allow earlier cessation of medication and guide appropriate treatment durations.
PubMed: 38800312
DOI: 10.7759/cureus.58872 -
Cureus Apr 2024Aluminum phosphide (ALP) poisoning poses a significant public health concern worldwide, with a high mortality rate and no established definitive treatment. This case...
Aluminum phosphide (ALP) poisoning poses a significant public health concern worldwide, with a high mortality rate and no established definitive treatment. This case report highlights a 30-year-old male with G6PD deficiency who ingested ALP tablets, presenting with jaundice and anemia. Despite the severity of ALP poisoning, the concurrent G6PD deficiency appeared to confer a protective effect, potentially mitigating complications. Laboratory investigations revealed characteristic findings, including unconjugated hyperbilirubinemia and normocytic hypochromic anemia. Treatment involved supportive measures and transfusion, leading to clinical improvement and discharge. The discussion focuses on the pathophysiology of G6PD deficiency and its protective role against ALP poisoning, supported by a literature review and experimental evidence. Moreover, potential therapeutic interventions targeting oxidative stress are discussed. This case underscores the importance of considering G6PD deficiency in ALP poisoning management and highlights avenues for further research into protective mechanisms and treatment strategies.
PubMed: 38800224
DOI: 10.7759/cureus.58888 -
Frontiers in Immunology 2024The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial...
BACKGROUND
The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC.
MATERIALS AND METHODS
Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs).
RESULTS
A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7-30.1) and the median PFS was 11.9 months (95% CI, 6.7-17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs.
CONCLUSION
Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.
Topics: Humans; Male; Antineoplastic Combined Chemotherapy Protocols; Female; Phenylurea Compounds; Middle Aged; Quinolines; Aged; Cholangiocarcinoma; Antibodies, Monoclonal; Bile Duct Neoplasms; Infusions, Intra-Arterial; Leucovorin; Adult; Fluorouracil; Treatment Outcome; Organoplatinum Compounds; Hepatic Artery; Retrospective Studies
PubMed: 38799453
DOI: 10.3389/fimmu.2024.1397827 -
Nutrients May 2024Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication,...
Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication, developing and designing antidotes with superior detoxification capacity and revealing their underlying mechanisms remains a major challenge. Therefore, we developed the first next-generation probiotic -pSK18a-MT that delivers metallothionein (MT) to overcome Cd-induced liver injury in C57BL/6 mice by utilizing bacterial surface display technology. The results demonstrate that -pSK18a-MT could efficiently express MT without altering the growth and probiotic properties of the strain. Moreover, we found that -pSK18a-MT ameliorated Cd contamination-induced hepatic steatosis, inflammatory cell infiltration, and liver fibrosis by decreasing the expression of aminotransferases along with inflammatory factors. Activation of the Nrf2-Keap1 signaling pathway also further illustrated the hepatoprotective effects of the engineered bacteria. Finally, we showed that -pSK18a-MT improved the colonic barrier function impaired by Cd induction and ameliorated intestinal flora dysbiosis in Cd-poisoned mice by increasing the relative abundance of the Verrucomicrobiota. These data revealed that the combination of and MT both alleviated Cd-induced liver injury to a greater extent and restored the integrity of colonic epithelial tissues and bacterial dysbiosis.
Topics: Animals; Probiotics; Gastrointestinal Microbiome; Escherichia coli; Metallothionein; Mice, Inbred C57BL; Cadmium; Mice; Chemical and Drug Induced Liver Injury; Dysbiosis; Male; Liver; Signal Transduction
PubMed: 38794706
DOI: 10.3390/nu16101468