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Ovarian adenocarcinoma is the gynecological malignancy with the worst prognosis and the highest mortality rate. In the first stages of treatment, chemotherapy results effective, but its prolonged use and high doses lead to the appearance of resistance to treatments and relapse in most patients, representing a major challenge for clinicians. We developed PEP-010, a cell penetrating proapoptotic peptide disrupting the protein-protein interaction between caspase-9 and protein phosphatase 2A, thereby leading to the recovery of their activity in the apoptotic pathway. MTT assay or Annexin-V/Propidium Iodide staining and flow cytometry analysis were used to assess sensitivity to chemotherapies and apoptosis after treatment with PEP-010 in monotherapy or in combination with paclitaxel in ovarian carcinoma cell lines. DNA damage was assessed by immunofluorescence using γH2AX marker. We show here that PEP-010 effectively induces cell death in monotherapy on in up to 55% of cells from ovarian adenocarcinoma cell models resistant to different chemotherapies. Moreover, when used in combination with paclitaxel, one of the therapeutic options for recurrent ovarian carcinoma, PEP-010 showed a beneficial effect leading to the reduction of the IC50 of paclitaxel of 2.2 times and to apoptosis in 87% of cells. The described results suggest the potential therapeutic interest for PEP-010 and lead to the choice of ovarian adenocarcinoma as one of the major indications of the ongoing clinical trial. [ABSTRACT FROM AUTHOR]

Background: As the development of novel anti-angiogenic drugs and the continuous evolution of guideline recommendations, the efficacy and safety of anti-angiogenic agents in ovarian cancer (OC) remains unclear. Consequently, a meta-analysis was carried out to assess the efficacy and safety of antiangiogenic drug monotherapy and combination therapy for OC. Methods: An exhaustive literature review was performed across multiple databases, including PubMed, Embase, Web of Science, and Cochrane, encompassing all relevant randomized controlled trials (RCTs) up until 6 April 2024. The evaluation of efficacy outcomes incorporated progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Safety was assessed through the occurrence of any grade adverse events (AEs) and grade ≥3 AEs. Synthesis of the data involved the calculation of hazard ratios (HRs), relative risks (RRs), and their corresponding 95% confidence intervals (CIs) and prediction intervals (PIs). Trial sequential analysis was executed employing TSA v0.9.5.10 Beta software, STATA 12.0, and R software 4.3.1. Results: In this meta-analysis, 35 RCTs were included, encompassing 16,199 subjects in total. The overall analysis indicated that anti-angiogenic drug combination therapy significantly improved PFS (HR [95% CI] = 0.678 [0.606–0.759], 95% PI: 0.415–1.108), OS (HR [95% CI] = 0.917 [0.870–0.966], 95% PI: 0.851–0.984), and ORR (RR [95% CI] = 1.441 [1.287–1.614], 95% PI: 1.032–2.014), but also increased the incidence of grade ≥3 AEs (RR [95% CI] = 1.137 [1.099–1.177], 95% PI: 1.011–1.252). The analysis did not corroborate any benefit of anti-angiogenic monotherapy over placebo concerning PFS (HR [95% CI] = 0.956 [0.709–1.288], 95% PI: 0.345–2.645) and OS (HR [95% CI] = 1.039 [0.921–1.173], 95% PI: 0.824–1.331). However, it was observed that monotherapy with anti-angiogenic drugs did increase the incidence of any grade AEs (RR [95% CI] = 1.072 [1.036–1.109], 95% PI: 0.709–1.592). Conclusion: Our study confirmed the PFS, OS, and ORR benefits of antiangiogenic drug combination therapy for OC patients. The efficacy results of anti-angiogenic monotherapy necessitates further evaluation as more RCTs become available. Clinicians should be vigilant of AEs when administering antiangiogenic agents in a clinical setting. [ABSTRACT FROM AUTHOR]

ObjectiveThere is currently no consensus on whether the combination therapy of Vitamin D (VitD) and bisphosphonates offers superior efficacy compared to monotherapy in the treatment of postmenopausal osteoporosis. The aim of this study is to conduct a meta-analysis of recent relevant research to synthesize the available evidence and further investigate whether the combined use of VitD and bisphosphonates is superior to monotherapy in treating osteoporosis in postmenopausal women.Methods and resultsWe systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized controlled trials (RCTs) comparing the effects of monotherapy with VitD or bisphosphonates versus their combination therapy in the treatment of postmenopausal osteoporosis, up to 1 February 2024. The articles were independently screened and relevant data were extracted by two investigators. The changes in mean values and percentage changes for bone resorption markers, bone formation markers, bone mineral density, and bone mineral metabolism markers were expressed using the standardized mean difference (SMD) and 95% confidence intervals (CI). Heterogeneity was quantitatively described using the I2 test. Subsequently, sensitivity analyses were performed for data with significant heterogeneity. Subgroup analyses were conducted based on the type of monotherapy used, and potential publication bias was assessed. The analysis revealed that the combination of VitD and bisphosphonates demonstrated a more pronounced effect in increasing alkaline phosphatase (ALP), 25-hydroxyvitamin D (25-OH-VD), and serum calcium (sCa) levels, as well as in decreasing levels of serum bone-specific alkaline phosphatase (sBALP), serum C-terminal telopeptide of type I collagen (sCTX), and urinary N-telopeptide of type I collagen (UriNTX) compared to the monotherapy group. However, the combination of VitD and bisphosphonates did not show a significant advantage over monotherapy in terms of improving osteocalcin levels. The differences in the mean changes in osteocalcin, UriNTX, and sCa, as well as the percentage changes in parathyroid hormone (PTH) were not statistically significant (p > 0.05).ConclusionThe meta-analysis suggests that compared to monotherapy, the combination therapy of VitD and bisphosphonates exhibits a more favorable effect on bone mineral density and bone calcium metabolism-related markers in the treatment of postmenopausal osteoporosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/PROSPERO

BackgroundEpilepsy management during pregnancy is crucial for both the mother and fetus. The use of antiseizure medications (ASMs) during pregnancy requires careful consideration due to their potential effects on maternal and fetal health.MethodsThis study analyzed trends in ASMs use among pregnant people in four Canadian provinces over 20 years (Manitoba, Saskatchewan, Alberta, and Quebec). Descriptive statistics were utilized to examine the characteristics of the population, with the frequency and patterns of ASM use estimated throughout each trimester. Linear regression models were developed to analyze yearly patterns of ASM utilization for the overall study population, as well as for people with and without epilepsy.ResultsAmong 1,317,141 pregnant individuals across four provinces, 0.7% had epilepsy. Of the total pregnancies, 1.7% (n = 22,783) were exposed to ASMs, comprising 4,392 from pregnant people with epilepsy (PPWE) and 18,391 from those without epilepsy (PPWOE). Results demonstrated varying trends in ASM usage between provinces, with an overall increase in usage among people without epilepsy in Manitoba, Saskatchewan, and Alberta. ASM use among PPWOE surged significantly in Manitoba (24.2–149.1 per 10,000 pregnant people), Saskatchewan (29.4–107.0 per 10,000), and Alberta (65.7–241.7 per 10,000) (p < 0.05). In Alberta, PPWE’s ASM exposure also rose, from 23.6 in 2008 to 43.0 per 10,000 pregnant people in 2021, while Quebec witnessed a decrease from 59.2 in 1998 to 45.5 per 10,000 pregnancies in 2015. Analysis of ASM use by trimester illustrated a substantial decline among PPWOE from 365 days pre-pregnancy to the third trimester in all provinces. ASM utilization by drug class showcased significant shifts, with second-generation ASMs experiencing a notable rise. Carbamazepine, once prominent, declined, making way for lamotrigine. Regional variations underscore diverse preferences, such as clonazepam’s sustained popularity in Manitoba and Quebec.ConclusionThe study identified increasing trends in ASM use, particularly the increased use of second-generation ASMs, and differences in prescription patterns for pregnant individuals with and without epilepsy. These findings reveal changing ASM use patterns, including increased second-generation ASM use and regional disparities, providing valuable insights into real-world prescription practices.

Pregnancy-related gastric cancer is characterized by a refractory nature and poor prognosis; few gastric cancer cases during pregnancy achieved acceptable outcomes by using anti-PD-1 as a monotherapy. A 32-year-old pregnant female patient was admitted to the emergency department of the obstetrics and gynecology department and eventually diagnosed with gastric cancer. Radical surgery for gastric cancer was conducted after the termination of pregnancy. At 1-year postoperative follow-up, tumor recurrence was revealed. This patient has achieved a decrease in tumor burden after receiving anti-PD-1 as a monotherapy. This case documents tumor response to PD-1 monotherapy in pregnancy-related gastric cancer and highlights the potential for future use in specific clinical scenarios. [ABSTRACT FROM AUTHOR]

Ovarian adenocarcinoma is the gynecological malignancy with the worst prognosis and the highest mortality rate. In the first stages of treatment, chemotherapy results effective, but its prolonged use and high doses lead to the appearance of resistance to treatments and relapse in most patients, representing a major challenge for clinicians. We developed PEP-010, a cell penetrating proapoptotic peptide disrupting the protein-protein interaction between caspase-9 and protein phosphatase 2A, thereby leading to the recovery of their activity in the apoptotic pathway. MTT assay or Annexin-V/Propidium Iodide staining and flow cytometry analysis were used to assess sensitivity to chemotherapies and apoptosis after treatment with PEP-010 in monotherapy or in combination with paclitaxel in ovarian carcinoma cell lines. DNA damage was assessed by immunofluorescence using γH2AX marker. We show here that PEP-010 effectively induces cell death in monotherapy on in up to 55% of cells from ovarian adenocarcinoma cell models resistant to different chemotherapies. Moreover, when used in combination with paclitaxel, one of the therapeutic options for recurrent ovarian carcinoma, PEP-010 showed a beneficial effect leading to the reduction of the IC50 of paclitaxel of 2.2 times and to apoptosis in 87% of cells. The described results suggest the potential therapeutic interest for PEP-010 and lead to the choice of ovarian adenocarcinoma as one of the major indications of the ongoing clinical trial.

BackgroundLevetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however, no consensus exists on applying LEV monotherapy among children with epilepsy.ObjectiveThe present work focused on comparing the efficacy and safety of LEV and OXC monotherapy in treating children with epilepsy.MethodsWe conducted a comprehensive search across multiple databases including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, VIP, and China Biology Medicine disc, covering studies from inception to August 26, 2023. We included randomized controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of LEV and OXC monotherapy for treating epilepsy in children. We utilized Cochrane Risk of Bias Tool in RevMan 5.3 software for assessing included RCTs quality. In addition, included cohort studies quality was determined using Newcastle-Ottawa Scale (NOS). A random-effects model was utilized to summarize the results.ResultsThis meta-analysis included altogether 14 studies, including 893 children with epilepsy. LEV and OXC monotherapy was not statistical different among children with epilepsy in seizure-free rate (relative risk [RR] = 1.010, 95% confidence interval [CI] [0.822, 1.242], P > 0.05) and seizure frequency decrease of ≥50% compared with baseline [RR = 0.938, 95% CI (0.676, 1.301), P > 0.05]. Differences in total adverse reaction rate [RR = 1.113, 95% CI (0.710, 1.744), P > 0.05] and failure rate because of serious adverse reaction [RR = 1.001, 95% CI (0.349, 2.871), P > 0.05] were not statistical different between LEV and OXC treatments among children with epilepsy. However, the effects of OXC monotherapy on thyroid among children with epilepsy was statistically correlated than that of LEV (thyroid stimulating hormone: standardized mean difference [SMD] = −0.144, 95% CI [−0.613, 0.325], P > 0.05; free thyroxine: SMD = 1.663, 95% CI [0.179, 3.147], P

Introduction: Immune checkpoint inhibitors (ICIs) exert antitumor responses in many types of cancer but may also induce serious or fatal toxicities that affect all organ systems, including the hematologic and lymphatic systems. However, the risk of hematologic and lymphatic system toxicities following different ICI treatments remains unknown. This study aimed to describe the hematologic and lymphatic system toxicities associated with different ICI regimens and the impact of combining ICIs with anti-vascular endothelial growth factor drugs using the United States Food and Drug Administration Adverse Event Reporting System pharmacovigilance database. Methods: The reporting odds ratio (ROR) and information component (IC) indices were used to identify disproportionate reporting of ICI-associated hematologic and lymphatic adverse events (AEs). Results: We extracted 10,971 ICI-associated hematologic and lymphatic AEs from 35,417,155 reports. These AEs were more frequently reported in female patients (ROR: 1.04 95% confidence interval [CI]: 1.01–1.07) and younger patients (ROR: 1.05 95% CI: 1.01–1.09). The disseminated intravascular coagulation fatality rate (63.97%) was the highest among the reported preferred terms, despite its low incidence (3.32%). The time to onset of ICIrelated hematologic and lymphatic AEs was relatively short, with 77.44% reported within 3 months. Disproportionate analysis showed that most ICIs were associated with significant overreporting of hematologic and lymphatic AEs (IC025: 0.34 and ROR025: 2.10). Hematologic and lymphatic system AEs were more frequently reported in patients treated with anti-programmed cell death protein 1/programmed cell death ligand 1 monotherapy than in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 monotherapy (ROR: 1.54, 95% CI: 1.38–1.71), with atezolizumab showing the strongest signal (ROR025: 4.19, IC025: 1.00). In patients receiving combined treatment, ICIs plus bevacizumab exerted a higher disproportion signal than monotherapy (ROR: 161, 95% CI: 1.75–1.88). Discussion: The spectrum of hematologic and lymphatic AEs differed according to the ICI regimen. Early recognition and management of ICI-related hematologic and lymphatic AEs are vital in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Studies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop resistance to NAA therapy, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib in combination with NAA may become a promising therapy. However the overall benefit of olaparib monotherapy or combination therapy still needs to be evaluated. Therefore, we performed a network meta-analysis to assess the efficacy and toxicity between olaparib, olaparib combined with abiraterone and NAA. Methods: We searched PubMed, EMBASE, the Cochrane Library and American Society of Clinical Oncology (ASCO) University Meeting abstracts for randomized controlled trials reporting olaparib and NAA from 2010 up to March, 2023. Network meta-analysis using Stata 16.0 and R 4.4.2, hazard ratios (HR) with 95% confidence intervals (CI) were used to assess the results. Results: Four trials reported olaparib, olaparib plus abiraterone and apalutamide plus abiraterone. radiographic progression-free survival (rPFS) was significantly lower in patients on apalutamide plus abiraterone compared to olaparib (HR, 1.43; 95% CI, 1.06-1.93). rPFS was similar for olaparib plus abiraterone and olaparib (HR, 1.35; 95% CI, 0.99-1.84); likewise, olaparib plus abiraterone and apalutamide plus abiraterone were similar (HR, 1.06; 95% CI, 0.83-1.35). In addition, there was no significant difference between the three interventions for OS. But olaparib has the highest probability of being a preferred treatment for improving rPFS and OS. Conclusion: rPFS was in favor of olaparib compared with apalutamide plus abiraterone. But there were no difference between olaparib plus abiraterone and either olaparib or apalutamide plus abiraterone. Apalutamide plus abiraterone might be the most preferred intervention in cases where AEs are involved. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) persists in latently infected CD4+T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (ACC008) are described. It is interestingly to note that the lack of the multipass transmembrane proteins serine incorporator 3 (SERINC3) and the multipass transmembrane proteins serine incorporator 5 (SERINC5) may be one of the reasons for the enhanced infectivity of HIV-1. This discovery of SERINC3 and SERINC5 provides new ideas for HIV-1 medication development. Therefore, we believe that in treating AIDS, antiviral medications should be rationally selected for pre-exposure and postexposure prophylaxis to avoid the emergence of drug resistance. Attention should be paid to the research and development of new drugs to predict HIV mutations as accurately as possible and to develop immune antibodies to provide multiple guarantees for the cure of AIDS. [ABSTRACT FROM AUTHOR]

In chronic lymphocytic leukaemia (CLL), immune dysregulation is common and can manifest as immune thrombocytopenia (ITP). Corticosteroids are the mainstay for front-line management of CLL-associated ITP. Therapy refractoriness represents a clinical challenge and is an indication to commence CLL-directed treatment, historically with anti-CD20 antibody-based chemoimmunotherapy. There is a small but growing body of evidence supporting the use of Bruton's tyrosine kinase (BTK) inhibitors in this setting, but not the B-cell lymphoma-2 inhibitor, venetoclax. Here, we describe two cases of refractory ITP in patients with CLL who successfully achieved and sustained complete remission with fixed-duration venetoclax monotherapy. Responses were rapid and durable and not explained by the concomitant use of an anti-CD20 antibody. This supports a dual role for single-agent venetoclax in managing active CLL and associated ITP as an alternative to BTK inhibitors and anti-CD20 monoclonals. [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%--87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696 [ABSTRACT FROM AUTHOR]

Background: Clozapine is considered one of the most effective antipsychotic drugs, but it is most likely to cause metabolic abnormalities. Researchers have studied the causes of metabolic abnormalities caused by clozapine from multiple perspectives, but the reasons remain unclear. Purpose: Characterize the gut microbiota of people with schizophrenia taking clozapine, exploring the association between gut microbiota and glucose lipid metabolic markers in schizophrenia patients taking clozapine. Research design: Sixty-one long-term inpatients with schizophrenia in clozapine monotherapy were selected as study subjects. We got four subgroups by sex and the presence of metabolic syndrome. Data analysis: 16s analysis technology was applied at the genus level to determine the classification of gut microbiota. Then we compared the characteristics of gut microbiota and the association of gut microbiota with glucose lipid metabolic markers in each group. Findings: We found differences in the diversity of gut microbiota among groups. The association between gut microbiota and glucose lipid metabolic markers was complicated. Gender was an important differentiating factor. Oscillibacter has a low abundance. However, it was the only genus associated with glycemic or lipids in each group. Among metabolic syndromes, Gemmiger was positively correlated with most lipids in females but negatively correlated in males, showing gender differences. In female non-metabolic syndromes, Bifidobacterium lost its probiotic character; instead, showing pathogenicity, which has strong positive correlations with fasting blood glucose and low-density lipoprotein but negative correlations with Apolipoprotein A1. Maybe schizophrenia, taking clozapine, and gender factors influenced the gut microbiota, which complicated our findings. The significance of the results remains to be determined by in-depth studies. [ABSTRACT FROM AUTHOR]

In chronic lymphocytic leukaemia (CLL), immune dysregulation is common and can manifest as immune thrombocytopenia (ITP). Corticosteroids are the mainstay for front-line management of CLL-associated ITP. Therapy refractoriness represents a clinical challenge and is an indication to commence CLL-directed treatment, historically with anti-CD20 antibody-based chemoimmunotherapy. There is a small but growing body of evidence supporting the use of Bruton’s tyrosine kinase (BTK) inhibitors in this setting, but not the B-cell lymphoma-2 inhibitor, venetoclax. Here, we describe two cases of refractory ITP in patients with CLL who successfully achieved and sustained complete remission with fixed-duration venetoclax monotherapy. Responses were rapid and durable and not explained by the concomitant use of an anti-CD20 antibody. This supports a dual role for single-agent venetoclax in managing active CLL and associated ITP as an alternative to BTK inhibitors and anti-CD20 monoclonals.

IntroductionCarbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate in vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alone against CRE and/or MDR-PA isolates or infections.MethodsWe systematically reviewed the relevant literature in CINAHL/MEDLINE, Pubmed, Cochrane, Web of Science, Embase, and Scopus until December 1, 2022. Review articles, grey literature, abstracts, comments, editorials, non-peer reviewed articles, non-English articles, and in vitro synergy studies conducted on single isolates were excluded.Results22 in vitro, 7 in vivo and 20 clinical studies were evaluated. In vitro studies showed reliable synergy between CZA and aztreonam against metallo-β-lactamase (MBL)-producing isolates. Some studies indicated good in vitro synergy between CZA and amikacin, meropenem, fosfomycin and polymyxins against CRE isolates. For MDR-PA isolates, there are comparatively fewer in vitro or in vivo studies. In observational clinical studies, mortality, clinical cure, adverse events, and development of CZA resistance after exposure were generally similar in monotherapy and combination therapy groups. However, antibiotic-related nephrotoxicity and infection relapses were higher in patients receiving CZA combination therapies.DiscussionThe benefit, if any, of CZA combination regimens in MDR-PA infections is elusive, as very few clinical studies have included these infections. There is no currently documented clinical benefit for the use of CZA combination regimens rather than CZA monotherapy. CZA combined with aztreonam for serious infections due to MBL producers should be evaluated by randomized controlled trials.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278552, CRD42021278552.

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP). Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up = 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes. Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30-7.01) and 10.38 letters (95% CI = 8.02-12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm(95% CI = from -154.99 to -109.90) and 213.93 µm (95% CI = from -280.04 to -147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2-5.6) and 2.8 injections (95% CI = 1.3-4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes. Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP).Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes.Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30–7.01) and 10.38 letters (95% CI = 8.02–12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm (95% CI = from −154.99 to −109.90) and 213.93 µm (95% CI = from −280.04 to −147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2–5.6) and 2.8 injections (95% CI = 1.3–4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes.Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy.

Background: We aim to evaluate the efficacy and tolerability of Janus kinase inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in active rheumatoid arthritis (RA). Methods: Medline, EMBASE, and Cochrane Library were systematically searched to identify relevant randomized controlled trials (RCTs). Pooled analysis was conducted using random-effects model, along with the risk difference (RD) and 95% confidence intervals (CIs). Results: Three RCTs, including 2,290 patients, were included. JAKi (tofacitinib, baricitinib, and filgotinib) plus MTX displayed a higher proportion of patients meeting the American College of Rheumatology (ACR) criteria than JAKi alone at week 52 (ACR20 RD 0.032; 95% CI −0.027 to 0.091; ACR50 RD 0.050; 95% CI 0.003 to 0.097; ACR70 RD 0.056; 95% CI 0.012 to 0.100). Similar results were observed for ACR20/50/70 at week 24. No significant difference was found between two regimens for the proportion of patients achieving Health Assessment Questionnaire disability index (HAQ-DI) improvement ≥ 0.22 at weeks 24 and 52. Regarding low disease activity and remission achievement, JAKi in combination with MTX, contributed higher response rates than JAKi alone at weeks 24 and 52. Compared with JAKi monotherapy, combination therapy had a higher risks of treatment-emergent adverse events (TEAEs) and adverse events (AEs) leading to study discontinuation. Conclusion: JAKi combined with MTX demonstrated superiority to JAKi monotherapy in terms of ACR responses, low disease activity and remission achievement. The two regimens presented comparable physical functioning measured by HAQ-DI improvement and similar tolerability, except for high risks of TEAEs and AEs leading to study discontinuation in combination therapy. [ABSTRACT FROM AUTHOR]

Background: Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations. Methods: Through an updated meta-analysis, studies included were valued by the Cochrane Evaluation Manual and Robins-I. Biochemical and clinical indicator changes in UDCA-refractory PBC patients receiving combination therapy were analyzed by Revman 5.42. Then, we explored the influence of fenofibrate dose and the effectiveness and safety of long-term application by retrospective cohort study. Results: Our meta-analysis included nine publications with a total of 389 patients, including 216 treated with UDCA alone and 173 who received combination therapy. The meta-analysis showed that combination therapy was more effective than UDCA monotherapy in decreasing biochemical parameters, such as ALP, GGT, IgM, and TG. However, the occurrence of pruritus and adverse events was slightly higher with combination therapy than with UDCA monotherapy. A total of 156 patients were included in our cohort study: 68 patients underwent UDCA monotherapy, and 88 patients underwent combination therapy. Among UDCA-refractory patients, fenofibrate add-on therapy significantly improved the ALP normalization rate. Conclusion: The combination of fenofibrate and UDCA can decrease biochemical parameters, of UDCA-refractory PBC patient. Furthermore, the efficacy and safety of long-term combination therapy were also confirmed in our cohort study. [ABSTRACT FROM AUTHOR]

Objective: A personalized simulation tool, p-THYROSIM, was developed (1) to better optimize replacement LT4 and LT4+LT3 dosing for hypothyroid patients, based on individual hormone levels, BMIs, and gender; and (2) to better understand how gender and BMI impact thyroid dynamical regulation over time in these patients. Methods: p-THYROSIM was developed by (1) modifying and refining THYROSIM, an established physiologically based mechanistic model of the system regulating serum T3, T4, and TSH level dynamics; (2) incorporating sex and BMI of individual patients into the model; and (3) quantifying it with 3 experimental datasets and validating it with a fourth containing data from distinct male and female patients across a wide range of BMIs. For validation, we compared our optimized predictions with previously published results on optimized LT4 monotherapies. We also optimized combination T3+T4 dosing and computed unmeasured residual thyroid function (RTF) across a wide range of BMIs from male and female patient data. Results: Compared with 3 other dosing methods, the accuracy of p-THYROSIM optimized dosages for LT4 monotherapy was better overall (53% vs. 44%, 43%, and 38%) and for extreme BMI patients (63% vs. ~51% low BMI, 48% vs. ~36% and 22% for high BMI). Optimal dosing for combination LT4+LT3 therapy and unmeasured RTFs was predictively computed with p-THYROSIM for male and female patients in low, normal, and high BMI ranges, yielding daily T3 doses of 5 to 7.5 mg of LT3 combined with 62.5-100 mg of LT4 for women or 75-125 mg of LT4 for men. Also, graphs of steady-state serum T3, T4, and TSH concentrations vs. RTF (range 0%-50%) for untreated patients showed that neither BMI nor gender had any effect on RTF predictions for our patient cohort data. Notably, the graphs provide a means for estimating unmeasurable RTFs for individual patients from their hormone measurements before treatment. Conclusions: p-THYROSIM can provide accurate monotherapies for male and female hypothyroid patients, personalized with their BMIs. Where combination therapy is warranted, our results predict that not much LT3 is needed in addition to LT4 to restore euthyroid levels, suggesting opportunities for further research exploring combination therapy with lower T3 doses and slow-releasing T3 formulations. [ABSTRACT FROM AUTHOR]

In this paper, we address the problem of optimal thyroid hormone replacement strategy development for hypothyroid patients. This is challenging for the following reasons. First, it is difficult to determine the correct dosage leading to normalized serum thyroid hormone concentrations of a patient. Second, it remains unclear whether a levothyroxine L - T 4) monotherapy or a liothyronine/levothyroxine (L - T 3/ L - T 4) combined therapy is more suitable to treat hypothyroidism. Third, the optimal intake frequency of L - T 3/ L - T 4 is unclear. We address these issues by extending a mathematical model of the pituitary-thyroid feedback loop to be able to consider an oral intake of L - T 3/ L - T 4. A model predictive controller (MPC) is employed to determine optimal dosages with respect to the thyroid hormone concentrations for each type of therapy. The results indicate that the L - T 3/ L - T 4 combined therapy is slightly better (in terms of the achieved hormone concentrations) to treat hypothyroidism than the L - T 4 monotherapy. In case of a specific genetic variant, namely genotype CC in polymorphism rs2235544 of gene DIO1 , the simulation results suggest that the L - T 4 monotherapy is better to treat hypothyroidism. In turn, when genotype AA is considered, the L - T 3/ L - T 4 combined therapy is better to treat hypothyroidism. Furthermore, when genotype CC of polymorphism rs225014 (also referred to as c.274A>G or p.Thr92Ala) in the DIO2 gene is considered, the outcome of the L - T 3/ L - T 4 combined therapy is better in terms of the steady-state hormone concentrations (for a triiodothyronine setpoint at the upper limit of the reference range of healthy individuals). Finally, the results suggest that two daily intakes of L - T 3 could be the best trade-off between stable hormone concentrations and inconveniences for the patient. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is an important cause of cancer death and is considered the 3rd most lethal around the world. Hepatectomy, liver transplantation, and ablation therapy are considered curative treatments for early-stage HCC. Transarterial chemoembolization is the preferred therapy for intermediate stage HCC. Ssystemic therapy is recommended for advanced HCC. For more than a decade, sorafenib and lenvatinib were used as the first-line treatment for the advanced HCC. For the great success of immunotherapy in melanoma and lung cancer, some immune-based treatments, such as immune checkpoint inhibitors (ICIs), have been applied in the treatment of HCC. The anti-programmed cell death protein 1 (PD1) antibodies, including nivolumab and pembrolizumab, have been approved by the Food and Drug Administration for sorafenib-pretreated patients. Moreover, due to the results of durable antitumor responses attained from the phase 3 trials, atezolizumab in combination with bevacizumab is now the standard therapy for advanced HCC. Recently, there are a lot of clinical trials involving the ICIs, as monotherapy or combination therapy, with tyrosine kinase inhibitors, antiangiogenic drugs, cytotoxic agents, and locoregional treatments, providing a promising outcome for advanced HCC. Thus, this review summarized the role of ICIs for HCC patients with monotherapy or combination therapy. The success and failures of monotherapy and combination therapy involving ICIs have provided advanced insights into HCC treatment and led to novel avenues to improve therapy efficacy in HCC. [ABSTRACT FROM AUTHOR]

Background: Discontinuation of antipsychotic treatment is a common problem in patients with schizophrenia and could reduce the effectiveness of treatment. Time to discontinuation (TTD) is one of the indicators of compliance and may also be an effective indicator of medication efficacy. The aim of the study was to compare the clinical effectiveness of quetiapine, olanzapine, risperidone, and aripiprazole in the real-world treatment of schizophrenia with 3-years follow-up. Method: A multi-center, open, cohort, prospective, real-world study was conducted. 706 patients were analyzed without intervention in medication selection and use, followed up for 3 years. Kaplan-Meier survival curves were used to draw the treatment discontinuation rates (TDR) curves at each time point. Cox proportional hazard regression model was used to assess the relative risk of TTD of antipsychotics. Results: There was a significant difference among monotherapy groups in all-cause antipsychotic treatment discontinuation (p = 0.0057). Among the four medications, the TDR of risperidone was the highest. Compared with polypharmacy, except for aripiprazole, the TDR of other three monotherapy medications were lower than that of polypharmacy, and olanzapine was statistically different (p = 0.0325). The cox regression analysis showed that after correction of Hochberg with multiple tests, only olanzapine had a relative risk lower than risperidone (p < 0.0083). Conclusions: The findings indicated that risperidone monotherapy and polypharmacy had the highest TDR and the shortest TTD. Olanzapine monotherapy had a relative risk lower than risperidone and was superior to polypharmacy. [ABSTRACT FROM AUTHOR]

Objective: We performed a prospective cohort study to compare the efficacy, safety, effect on mood, and quality of life between lamotrigine (LTG) and oxcarbazepine (OXC) monotherapy among Chinese adult patients with newly-diagnosed focal-onset epilepsy (FOE) with or without secondarily generalized tonic-clonic seizures. Methods: We enrolled 106 adult patients with new-onset FOE, of whom 56 were in the OXC group and 50 in the LTG group. Their clinical characteristics were detailly recorded especially basic seizure frequency, seizure types, and drug-related adverse events. Efficacy was evaluated as seizure-free (no seizure for 6 months), effective (seizure reduction by more than 50%), and ineffective (seizure reduction by less than 50%). Both intention-to-treat and per-protocol analyses were performed. We also assessed their mood state with the Zung Self-rating Scale for anxiety (Z-SAS) and Zung Self-rating Scale for Depression (Z-SDS) and quality of life (QOL) with Quality of Life in Epilepsy (QOLIE-31) at their baseline visit, 3-month visits, and 6-month visit. Intra-group comparisons in each group and inter-group comparisons between the two groups were made. Correlation analysis and multiple regression analysis were also conducted. Results: Except for gender, the two groups were well matched in any other characteristics such as primary seizure frequency and seizure types. In terms of efficacy, 33 patients in the OXC group were evaluated as seizure-free and 15 as effective, while in the LTG group, 31 were seizure-free, and nine were effective. No significant differences could be observed in efficacy between the two groups (P = 0.429). Through multiple logistic regression analysis, we found that OXC monotherapy was more likely to predict a seizure-free state (OR = 1.76) than LTG, but the difference didn't reach statistical significance (P = 0.322) after correcting for other clinical variables. Both groups had adverse events such as fatigue, drowsiness, dizziness, rash, and gastrointestinal discomfort, most of which were mild and transient. In the OXC group, the scores of SAS (P = 0.067) and SDS (P = 0.004) reduced at the 6-month visit, while the score of QOLIE-31 significantly increased (P = 0.001). In the LTG group, a significant decrease in SAS and SDS scores and an increase in QOLIE-31 scores could be witnessed (All P < 0.001). The inter-group comparison showed that improvement of SAS and SDS in the LTG group was more evident than that in the OXC group, which was of statistical significance. Correlational analysis indicated that the improvement of mood and life quality scales in both groups was independent of baseline seizure frequency and treatment efficacy. Multiple linear regression analysis indicated that LTG monotherapy was the only independent factor that could predict a better SAS (P = 0.01) and SDS (P = 0.019) outcome. Conclusions: OXC and LTG are effective as monotherapy and can be considered first-line selection among adult patients with new-onset FOE. Most adverse events are mild, transient, and tolerable. The two drugs improve the mood state of patients, though LTG is superior to OXC in this respect. OXC and LTG have great power in enhancing patients' quality of life. The positive effect on the psychosocial well-being of epilepsy patients may be one of the intrinsic pharmacological properties of LTG and OXC. [ABSTRACT FROM AUTHOR]

ObjectiveA personalized simulation tool, p-THYROSIM, was developed (1) to better optimize replacement LT4 and LT4+LT3 dosing for hypothyroid patients, based on individual hormone levels, BMIs, and gender; and (2) to better understand how gender and BMI impact thyroid dynamical regulation over time in these patients.Methodsp-THYROSIM was developed by (1) modifying and refining THYROSIM, an established physiologically based mechanistic model of the system regulating serum T3, T4, and TSH level dynamics; (2) incorporating sex and BMI of individual patients into the model; and (3) quantifying it with 3 experimental datasets and validating it with a fourth containing data from distinct male and female patients across a wide range of BMIs. For validation, we compared our optimized predictions with previously published results on optimized LT4 monotherapies. We also optimized combination T3+T4 dosing and computed unmeasured residual thyroid function (RTF) across a wide range of BMIs from male and female patient data.ResultsCompared with 3 other dosing methods, the accuracy of p-THYROSIM optimized dosages for LT4 monotherapy was better overall (53% vs. 44%, 43%, and 38%) and for extreme BMI patients (63% vs. ~51% low BMI, 48% vs. ~36% and 22% for high BMI). Optimal dosing for combination LT4+LT3 therapy and unmeasured RTFs was predictively computed with p-THYROSIM for male and female patients in low, normal, and high BMI ranges, yielding daily T3 doses of 5 to 7.5 μg of LT3 combined with 62.5–100 μg of LT4 for women or 75–125 μg of LT4 for men. Also, graphs of steady-state serum T3, T4, and TSH concentrations vs. RTF (range 0%–50%) for untreated patients showed that neither BMI nor gender had any effect on RTF predictions for our patient cohort data. Notably, the graphs provide a means for estimating unmeasurable RTFs for individual patients from their hormone measurements before treatment.Conclusionsp-THYROSIM can provide accurate monotherapies for male and female hypothyroid patients, personalized with their BMIs. Where combination therapy is warranted, our results predict that not much LT3 is needed in addition to LT4 to restore euthyroid levels, suggesting opportunities for further research exploring combination therapy with lower T3 doses and slow-releasing T3 formulations.

In this paper, we address the problem of optimal thyroid hormone replacement strategy development for hypothyroid patients. This is challenging for the following reasons. First, it is difficult to determine the correct dosage leading to normalized serum thyroid hormone concentrations of a patient. Second, it remains unclear whether a levothyroxine L-T4) monotherapy or a liothyronine/levothyroxine (L-T3/L-T4) combined therapy is more suitable to treat hypothyroidism. Third, the optimal intake frequency of L-T3/L-T4 is unclear. We address these issues by extending a mathematical model of the pituitary-thyroid feedback loop to be able to consider an oral intake of L-T3/L-T4. A model predictive controller (MPC) is employed to determine optimal dosages with respect to the thyroid hormone concentrations for each type of therapy. The results indicate that the L-T3/L-T4 combined therapy is slightly better (in terms of the achieved hormone concentrations) to treat hypothyroidism than the L-T4 monotherapy. In case of a specific genetic variant, namely genotype CC in polymorphism rs2235544 of gene DIO1, the simulation results suggest that the L-T4 monotherapy is better to treat hypothyroidism. In turn, when genotype AA is considered, the L-T3/L-T4 combined therapy is better to treat hypothyroidism. Furthermore, when genotype CC of polymorphism rs225014 (also referred to as c.274A>G or p.Thr92Ala) in the DIO2 gene is considered, the outcome of the L-T3/L-T4 combined therapy is better in terms of the steady-state hormone concentrations (for a triiodothyronine setpoint at the upper limit of the reference range of healthy individuals). Finally, the results suggest that two daily intakes of L-T3 could be the best trade-off between stable hormone concentrations and inconveniences for the patient.

Hepatocellular carcinoma (HCC) is an important cause of cancer death and is considered the 3rd most lethal around the world. Hepatectomy, liver transplantation, and ablation therapy are considered curative treatments for early-stage HCC. Transarterial chemoembolization is the preferred therapy for intermediate stage HCC. Ssystemic therapy is recommended for advanced HCC. For more than a decade, sorafenib and lenvatinib were used as the first-line treatment for the advanced HCC. For the great success of immunotherapy in melanoma and lung cancer, some immune-based treatments, such as immune checkpoint inhibitors (ICIs), have been applied in the treatment of HCC. The anti-programmed cell death protein 1 (PD1) antibodies, including nivolumab and pembrolizumab, have been approved by the Food and Drug Administration for sorafenib-pretreated patients. Moreover, due to the results of durable antitumor responses attained from the phase 3 trials, atezolizumab in combination with bevacizumab is now the standard therapy for advanced HCC. Recently, there are a lot of clinical trials involving the ICIs, as monotherapy or combination therapy, with tyrosine kinase inhibitors, antiangiogenic drugs, cytotoxic agents, and locoregional treatments, providing a promising outcome for advanced HCC. Thus, this review summarized the role of ICIs for HCC patients with monotherapy or combination therapy. The success and failures of monotherapy and combination therapy involving ICIs have provided advanced insights into HCC treatment and led to novel avenues to improve therapy efficacy in HCC.

ObjectiveWe performed a prospective cohort study to compare the efficacy, safety, effect on mood, and quality of life between lamotrigine (LTG) and oxcarbazepine (OXC) monotherapy among Chinese adult patients with newly-diagnosed focal-onset epilepsy (FOE) with or without secondarily generalized tonic-clonic seizures.MethodsWe enrolled 106 adult patients with new-onset FOE, of whom 56 were in the OXC group and 50 in the LTG group. Their clinical characteristics were detailly recorded especially basic seizure frequency, seizure types, and drug-related adverse events. Efficacy was evaluated as seizure-free (no seizure for 6 months), effective (seizure reduction by more than 50%), and ineffective (seizure reduction by less than 50%). Both intention-to-treat and per-protocol analyses were performed. We also assessed their mood state with the Zung Self-rating Scale for anxiety (Z-SAS) and Zung Self-rating Scale for Depression (Z-SDS) and quality of life (QOL) with Quality of Life in Epilepsy (QOLIE-31) at their baseline visit, 3-month visits, and 6-month visit. Intra-group comparisons in each group and inter-group comparisons between the two groups were made. Correlation analysis and multiple regression analysis were also conducted.ResultsExcept for gender, the two groups were well matched in any other characteristics such as primary seizure frequency and seizure types. In terms of efficacy, 33 patients in the OXC group were evaluated as seizure-free and 15 as effective, while in the LTG group, 31 were seizure-free, and nine were effective. No significant differences could be observed in efficacy between the two groups (P = 0.429). Through multiple logistic regression analysis, we found that OXC monotherapy was more likely to predict a seizure-free state (OR = 1.76) than LTG, but the difference didn't reach statistical significance (P = 0.322) after correcting for other clinical variables. Both groups had adverse events such as fatigue, drowsiness, dizziness, rash, and gastrointestinal discomfort, most of which were mild and transient. In the OXC group, the scores of SAS (P = 0.067) and SDS (P = 0.004) reduced at the 6-month visit, while the score of QOLIE-31 significantly increased (P = 0.001). In the LTG group, a significant decrease in SAS and SDS scores and an increase in QOLIE-31 scores could be witnessed (All P < 0.001). The inter-group comparison showed that improvement of SAS and SDS in the LTG group was more evident than that in the OXC group, which was of statistical significance. Correlational analysis indicated that the improvement of mood and life quality scales in both groups was independent of baseline seizure frequency and treatment efficacy. Multiple linear regression analysis indicated that LTG monotherapy was the only independent factor that could predict a better SAS (P = 0.01) and SDS (P = 0.019) outcome.ConclusionsOXC and LTG are effective as monotherapy and can be considered first-line selection among adult patients with new-onset FOE. Most adverse events are mild, transient, and tolerable. The two drugs improve the mood state of patients, though LTG is superior to OXC in this respect. OXC and LTG have great power in enhancing patients' quality of life. The positive effect on the psychosocial well-being of epilepsy patients may be one of the intrinsic pharmacological properties of LTG and OXC.

Background: Discontinuation of antipsychotic treatment is a common problem in patients with schizophrenia and could reduce the effectiveness of treatment. Time to discontinuation (TTD) is one of the indicators of compliance and may also be an effective indicator of medication efficacy. The aim of the study was to compare the clinical effectiveness of quetiapine, olanzapine, risperidone, and aripiprazole in the real-world treatment of schizophrenia with 3-years follow-up.Method: A multi-center, open, cohort, prospective, real-world study was conducted. 706 patients were analyzed without intervention in medication selection and use, followed up for 3 years. Kaplan-Meier survival curves were used to draw the treatment discontinuation rates (TDR) curves at each time point. Cox proportional hazard regression model was used to assess the relative risk of TTD of antipsychotics.Results: There was a significant difference among monotherapy groups in all-cause antipsychotic treatment discontinuation (p = 0.0057). Among the four medications, the TDR of risperidone was the highest. Compared with polypharmacy, except for aripiprazole, the TDR of other three monotherapy medications were lower than that of polypharmacy, and olanzapine was statistically different (p = 0.0325). The cox regression analysis showed that after correction of Hochberg with multiple tests, only olanzapine had a relative risk lower than risperidone (p < 0.0083).Conclusions: The findings indicated that risperidone monotherapy and polypharmacy had the highest TDR and the shortest TTD. Olanzapine monotherapy had a relative risk lower than risperidone and was superior to polypharmacy.

Aim: Evidence on the efficacy of combination treatment of teriparatide and denosumab for osteoporosis remains controversial. We aim to compare the efficacy between the combination treatment and monotherapy among patients with postmenopausal osteoporosis. Methods and results: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science up to 26 January 2022, for relevant studies. This meta-analysis reviewed all randomized controlled trials (RCTs) that reported on the combination treatment of teriparatide and denosumab in patients with postmenopausal osteoporosis. The articles were examined individually by two reviewers, and the relevant data was extracted. We combined weighted mean difference (WMD) for bone mineral density (BMD) using random- or fixed- effect models and conducted subgroup analyses. Sensitivity analyses were performed, and possible publication bias was also assessed. Overall, combination treatment enhanced the mean percent change of bone mineral density in lumbar spine than monotherapy (WMD = 2.91, 95%CI: 1.983.83; p = 0.00). And, combination treatment has been beneficial for enhancing the mean percent change of BMD in hip (WMD = 3.19, 95%CI: 2.25∼4.13; p = 0.00). There was no significant difference between combination treatment and monotherapy in terms of the adverse events (RR = 0.81, 95%CI: 0.45∼1.45; p = 0.472). Conclusion: The meta-analysis indicates that combination treatment led to greater BMD at the lumbar spine and hip in comparison to monotherapy, without an increased incidence of adverse events. Systematic Review Registration: (https://inplasy.com/), identifier (Inplasy Protocol 2734). [ABSTRACT FROM AUTHOR]

Background: Brain metastases from ovarian cancer are extremely rare and have a very poor prognosis. A multimodal approach (surgery combined with radiotherapy and chemotherapy) yields the best results in reducing neurological symptoms and prolonging survival. Unfortunately, not every patient receives a complete multimodal treatment due to their individual factors. Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as a maintenance treatment option for recurrent ovarian cancer. Using PARPi may prolong the overall survival in patients with brain metastases and recurrent ovarian cancer. Case Presentation: We report a case of a female patient with advanced ovarian cancer without any germline or somatic BRCA mutation. After 21 months, after reduction surgery and adjuvant chemotherapy, she was diagnosed with brain metastasis. Due to her physical fitness and economic situation, she did not receive any radiotherapy or chemotherapy but only received surgical debulking of the brain metastasis and niraparib maintenance treatment. Up to now, she has achieved a good treatment response, and the PFS is 29 months. Conclusion: Based on the response of our patient, PARP inhibitors as a single agent can probably be considered in patients with brain metastasis from ovarian cancer without BRCA mutation who cannot tolerate radiotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Although many novel regimens have entered the treatment paradigm for unresectable/metastatic BRAF V600-mutant melanoma, there is still a lack of head-to-head comparison in terms of security. We conducted a network meta-analysis to compare the risk of adverse events (AEs) across different treatments and to provide an acceptability ranking for patients. Methods: A systematic literature review was conducted in Embase, PubMed, WHO International Clinical Trials Registry Platform, and Clinical Trials.gov with a time frame from database inception to December 24, 2021. We retrieved evidence on the cumulative incidence of any-grade AEs means grades 1-5 AEs (regardless of severity) and severe AEs based on the pooled risk ratios (RRs) and 95% credible intervals (95% CrI). Results: Twelve publications and thirteen treatments enrolling 5,803 patients were included. For any-grade AEs, the acceptability of combined dabrafenib and trametinib is superior to the combination of vemurafenib and cobimetinib (RR: 0.94; Crl: 0.89, 0.98). Furthermore, nivolumab combined with ipilimumab increases any-grade AEs than single-agent ipilimumab (RR: 0.90; Crl: 0.83, 0.96) or nivolumab (RR: 0.90; Crl: 0.84, 0.97). For severe AEs, dabrafenib has the best acceptability than single-agent vemurafenib (RR: 0.66; Crl: 0.50, 0.87) or encorafenib (RR: 0.64; Crl: 0.43, 0.94). In addition, ipilimumab (SUCRA: 0.87) ranks first in the acceptability for any-grade AEs, and nivolumab (SUCRA: 0.95) ranks first in the acceptability for severe AEs. The ranking of the combination of vemurafenib and cobimetinib (SUCRA: 0.66) is superior to encorafenib in combination with binimetinib (SUCRA: 0.39) and combination of vemurafenib and cobimetinib (SUCRA: 0.18). Conclusions: We identified the lowest AE risk treatment options for BRAF V600-mutant melanoma patients. In general, immunotherapy (ipilimumab or nivolumab) has better acceptability than most targeted therapies, and triplet therapies are related with the worst acceptability. Moreover, single-agent dabrafenib can be used as the first choice in monotherapy, and the combination of dabrafenib and trametinib is the preferred combination therapy. Overall, the combination of immunotherapy drugs increases any-grade and severe AEs than a single agent, whereas the condition of targeted therapy drugs cannot be simply generalized. Therefore, this information can facilitate evidence-based decision-making and support optimizing treatment and outcomes in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: Evidence on the efficacy of combination treatment of teriparatide and denosumab for osteoporosis remains controversial. We aim to compare the efficacy between the combination treatment and monotherapy among patients with postmenopausal osteoporosis.Methods and results: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science up to 26 January 2022, for relevant studies. This meta-analysis reviewed all randomized controlled trials (RCTs) that reported on the combination treatment of teriparatide and denosumab in patients with postmenopausal osteoporosis. The articles were examined individually by two reviewers, and the relevant data was extracted. We combined weighted mean difference (WMD) for bone mineral density (BMD) using random- or fixed- effect models and conducted subgroup analyses. Sensitivity analyses were performed, and possible publication bias was also assessed. Overall, combination treatment enhanced the mean percent change of bone mineral density in lumbar spine than monotherapy (WMD = 2.91, 95%CI: 1.983.83; p = 0.00). And, combination treatment has been beneficial for enhancing the mean percent change of BMD in hip (WMD = 3.19, 95%CI: 2.25∼4.13; p = 0.00). There was no significant difference between combination treatment and monotherapy in terms of the adverse events (RR = 0.81, 95%CI: 0.45∼1.45; p = 0.472).Conclusion: The meta-analysis indicates that combination treatment led to greater BMD at the lumbar spine and hip in comparison to monotherapy, without an increased incidence of adverse events.Systematic Review Registration: (https://inplasy.com/), identifier (Inplasy Protocol 2734).

BackgroundAlthough many novel regimens have entered the treatment paradigm for unresectable/metastatic BRAF V600-mutant melanoma, there is still a lack of head-to-head comparison in terms of security. We conducted a network meta-analysis to compare the risk of adverse events (AEs) across different treatments and to provide an acceptability ranking for patients.MethodsA systematic literature review was conducted in Embase, PubMed, WHO International Clinical Trials Registry Platform, and Clinical Trials.gov with a time frame from database inception to December 24, 2021. We retrieved evidence on the cumulative incidence of any-grade AEs means grades 1-5 AEs (regardless of severity) and severe AEs based on the pooled risk ratios (RRs) and 95% credible intervals (95% CrI).ResultsTwelve publications and thirteen treatments enrolling 5,803 patients were included. For any-grade AEs, the acceptability of combined dabrafenib and trametinib is superior to the combination of vemurafenib and cobimetinib (RR: 0.94; Crl: 0.89, 0.98). Furthermore, nivolumab combined with ipilimumab increases any-grade AEs than single-agent ipilimumab (RR: 0.90; Crl: 0.83, 0.96) or nivolumab (RR: 0.90; Crl: 0.84, 0.97). For severe AEs, dabrafenib has the best acceptability than single-agent vemurafenib (RR: 0.66; Crl: 0.50, 0.87) or encorafenib (RR: 0.64; Crl: 0.43, 0.94). In addition, ipilimumab (SUCRA: 0.87) ranks first in the acceptability for any-grade AEs, and nivolumab (SUCRA: 0.95) ranks first in the acceptability for severe AEs. The ranking of the combination of vemurafenib and cobimetinib (SUCRA: 0.66) is superior to encorafenib in combination with binimetinib (SUCRA: 0.39) and combination of vemurafenib and cobimetinib (SUCRA: 0.18).ConclusionsWe identified the lowest AE risk treatment options for BRAF V600-mutant melanoma patients. In general, immunotherapy (ipilimumab or nivolumab) has better acceptability than most targeted therapies, and triplet therapies are related with the worst acceptability. Moreover, single-agent dabrafenib can be used as the first choice in monotherapy, and the combination of dabrafenib and trametinib is the preferred combination therapy. Overall, the combination of immunotherapy drugs increases any-grade and severe AEs than a single agent, whereas the condition of targeted therapy drugs cannot be simply generalized. Therefore, this information can facilitate evidence-based decision-making and support optimizing treatment and outcomes in clinical practice.

BackgroundBrain metastases from ovarian cancer are extremely rare and have a very poor prognosis. A multimodal approach (surgery combined with radiotherapy and chemotherapy) yields the best results in reducing neurological symptoms and prolonging survival. Unfortunately, not every patient receives a complete multimodal treatment due to their individual factors. Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as a maintenance treatment option for recurrent ovarian cancer. Using PARPi may prolong the overall survival in patients with brain metastases and recurrent ovarian cancer.Case PresentationWe report a case of a female patient with advanced ovarian cancer without any germline or somatic BRCA mutation. After 21 months, after reduction surgery and adjuvant chemotherapy, she was diagnosed with brain metastasis. Due to her physical fitness and economic situation, she did not receive any radiotherapy or chemotherapy but only received surgical debulking of the brain metastasis and niraparib maintenance treatment. Up to now, she has achieved a good treatment response, and the PFS is 29 months.ConclusionBased on the response of our patient, PARP inhibitors as a single agent can probably be considered in patients with brain metastasis from ovarian cancer without BRCA mutation who cannot tolerate radiotherapy and chemotherapy.

Background: Antipsychotics contribute to the development of type 2 diabetes mellitus (T2DM) in individuals with schizophrenia. However, the extent of the relationship between antipsychotic use and T2DM varies in different settings, and the magnitude of the drug-specific effects fluctuates widely. This study aimed to explore the association of T2DM with antipsychotic use among enrollees with schizophrenia in China's National Basic Public Health Service Program (NBPHSP) and the drug-specific relationship with T2DM among patients receiving antipsychotic monotherapy. Methods: We recruited diabetes-free patients with schizophrenia who were enrolled in the NBPHSP of Hunan Province from October 2009 to December 2018. The participants were classified into the following three groups: regular antipsychotic use, intermittent antipsychotic use, and antipsychotic-free groups. The patients were followed up until they received a T2DM diagnosis or until April 2019. Cox regression models were constructed to calculate the overall and drug-specific hazard ratios (HRs) to determine the antipsychotic–T2DM relationship. Interactive and subgroup analyses were performed to assess the heterogeneity of the effects across subgroups. Results: A total of 122,064 NBPHSP enrollees with schizophrenia were followed up for 1,507,829 cumulative person-years, and 2,313 (1.89%) patients developed T2DM. Patients who regularly and intermittently used antipsychotics had 117% (HR: 2.17, 95% CI: 1.83–2.57) and 53% (HR: 1.53, 95% CI: 1.23–1.90) higher risks of developing T2DM than antipsychotic-free patients, respectively. Regarding monotherapy, the T2DM risk increased by 66, 80, 62, and 64% after the regular use of clozapine, risperidone, chlorpromazine, and perphenazine, respectively. In addition, the antipsychotic-related risk of T2DM decreased as the patient's baseline body mass index, and baseline fasting plasma glucose level, as well as the dietary proportion of animal products, increased. Conclusion: Antipsychotics, especially clozapine, risperidone, chlorpromazine, and perphenazine, increased the T2DM risk among NBPHSP enrollees with schizophrenia. Mental health officers should accurately identify enrollees at a high risk of T2DM and take appropriate preventive measures to reduce the incidence of T2DM among patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA). Material and Methods: Between January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D'Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0. Results: Median age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D'Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS. Conclusion: Our long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA. [ABSTRACT FROM AUTHOR]

Introduction: Several maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients. Methods: MEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes. Results: We included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months. Conclusion: This study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the most common causes of blindness, thus seriously affecting people's health and quality of life. The topical medical therapy is as the first line treatment in the management of glaucoma since it is inexpensive, convenient, effective, and safe. This review summarizes and compares extensive clinical trials on the topical medications for the treatment of glaucoma, including topical monotherapy agents, topical fixed-combination agents, topical non-fixed combination agents, and their composition, mechanism of action, efficacy, and adverse effects, which will provide reference for optimal choice of clinical medication. Fixed-combination therapeutics offer greater efficacy, reliable security, clinical compliance, and tolerance than non-fixed combination agents and monotherapy agents, which will become a prefer option for the treatment of glaucoma. Meanwhile, we also discuss new trends in the field of new fixed combinations of medications, which may better control IOP and treat glaucoma. [ABSTRACT FROM AUTHOR]

BackgroundAntipsychotics contribute to the development of type 2 diabetes mellitus (T2DM) in individuals with schizophrenia. However, the extent of the relationship between antipsychotic use and T2DM varies in different settings, and the magnitude of the drug-specific effects fluctuates widely. This study aimed to explore the association of T2DM with antipsychotic use among enrollees with schizophrenia in China's National Basic Public Health Service Program (NBPHSP) and the drug-specific relationship with T2DM among patients receiving antipsychotic monotherapy.MethodsWe recruited diabetes-free patients with schizophrenia who were enrolled in the NBPHSP of Hunan Province from October 2009 to December 2018. The participants were classified into the following three groups: regular antipsychotic use, intermittent antipsychotic use, and antipsychotic-free groups. The patients were followed up until they received a T2DM diagnosis or until April 2019. Cox regression models were constructed to calculate the overall and drug-specific hazard ratios (HRs) to determine the antipsychotic–T2DM relationship. Interactive and subgroup analyses were performed to assess the heterogeneity of the effects across subgroups.ResultsA total of 122,064 NBPHSP enrollees with schizophrenia were followed up for 1,507,829 cumulative person-years, and 2,313 (1.89%) patients developed T2DM. Patients who regularly and intermittently used antipsychotics had 117% (HR: 2.17, 95% CI: 1.83–2.57) and 53% (HR: 1.53, 95% CI: 1.23–1.90) higher risks of developing T2DM than antipsychotic-free patients, respectively. Regarding monotherapy, the T2DM risk increased by 66, 80, 62, and 64% after the regular use of clozapine, risperidone, chlorpromazine, and perphenazine, respectively. In addition, the antipsychotic-related risk of T2DM decreased as the patient's baseline body mass index, and baseline fasting plasma glucose level, as well as the dietary proportion of animal products, increased.ConclusionAntipsychotics, especially clozapine, risperidone, chlorpromazine, and perphenazine, increased the T2DM risk among NBPHSP enrollees with schizophrenia. Mental health officers should accurately identify enrollees at a high risk of T2DM and take appropriate preventive measures to reduce the incidence of T2DM among patients with schizophrenia.

Glaucoma is one of the most common causes of blindness, thus seriously affecting people’s health and quality of life. The topical medical therapy is as the first line treatment in the management of glaucoma since it is inexpensive, convenient, effective, and safe. This review summarizes and compares extensive clinical trials on the topical medications for the treatment of glaucoma, including topical monotherapy agents, topical fixed-combination agents, topical non-fixed combination agents, and their composition, mechanism of action, efficacy, and adverse effects, which will provide reference for optimal choice of clinical medication. Fixed-combination therapeutics offer greater efficacy, reliable security, clinical compliance, and tolerance than non-fixed combination agents and monotherapy agents, which will become a prefer option for the treatment of glaucoma. Meanwhile, we also discuss new trends in the field of new fixed combinations of medications, which may better control IOP and treat glaucoma.

IntroductionTo evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA).Material and MethodsBetween January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D’Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0.ResultsMedian age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D’Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS.ConclusionOur long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA.

IntroductionSeveral maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients.MethodsMEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes.ResultsWe included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months.ConclusionThis study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness.

Background: The present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated. Methods: Numerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve. Results: The analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo. Conclusions: Overall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic. Systematic Review Registration: https://inplasy.com/inplasy-2021-6-0033/. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. Particularly, cases of bone metastasis have poorer prognoses. Case Presentation: A 62-year-old woman with suspected advanced HCC accompanied by bone metastasis with severe back pain and sciatica showed disease remission after cyproheptadine monotherapy. Initially, her serum alpha fetal protein (AFP) level was high, reaching up to 17697.62 ng/ml. A dose of 4 mg cyproheptadine, 3 times a day for 17 months was prescribed as the only treatment. Within 3 months, the serum AFP level gradually normalized down to 4.3 ng/ml. Both liver biopsy and bone biopsies were subsequently performed after 2 weeks of cyproheptadine. The results showed no malignancy. During the 34 months of follow-ups, the serum AFP remained normal in the range of 1.05 to 2.86 ng/ml. The patient has survived for 5 years without back pain and sciatica thus far. Conclusions: This is the first report to investigate a successful clinical approach in cyproheptadine monotherapy for an advanced HCC patient with bone metastasis. We recommend cyproheptadine as a potential anti-HCC agent for the treatment of HCC with bone metastasis, but more related studies such as prospectively clinical trials, and ideally randomized trials are still needed. [ABSTRACT FROM AUTHOR]

BackgroundThe present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated.MethodsNumerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve.ResultsThe analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo.ConclusionsOverall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic. Systematic Review Registrationhttps://inplasy.com/inplasy-2021-6-0033/.

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. Particularly, cases of bone metastasis have poorer prognoses.Case PresentationA 62-year-old woman with suspected advanced HCC accompanied by bone metastasis with severe back pain and sciatica showed disease remission after cyproheptadine monotherapy. Initially, her serum alpha fetal protein (AFP) level was high, reaching up to 17697.62 ng/ml. A dose of 4 mg cyproheptadine, 3 times a day for 17 months was prescribed as the only treatment. Within 3 months, the serum AFP level gradually normalized down to 4.3 ng/ml. Both liver biopsy and bone biopsies were subsequently performed after 2 weeks of cyproheptadine. The results showed no malignancy. During the 34 months of follow-ups, the serum AFP remained normal in the range of 1.05 to 2.86 ng/ml. The patient has survived for 5 years without back pain and sciatica thus far.ConclusionsThis is the first report to investigate a successful clinical approach in cyproheptadine monotherapy for an advanced HCC patient with bone metastasis. We recommend cyproheptadine as a potential anti-HCC agent for the treatment of HCC with bone metastasis, but more related studies such as prospectively clinical trials, and ideally randomized trials are still needed.

Introduction: Interest in the idea of recovery for certain patients with schizophrenia has been growing over the last decade. Improving symptomatology and functioning is crucial for achieving this. Our study aims to identify those factors that substantially contribute to real-world functioning in these patients.Methods: We carried out a cross-sectional study in stable outpatients with schizophrenia on maintenance antipsychotic monotherapy. Patients: We studied 144 outpatients with schizophrenia (DSM-IV-TR criteria) meeting the following criteria: (1) 18–65 years of age; (2) being clinically stable for at least the previous three months; (3) on maintenance antipsychotic monotherapy (prescriptions ≤ 10 mg olanzapine, ≤200 mg quetiapine, or ≤100 mg levomepromazine as hypnotics were also allowed); and (4) written informed consent. Assessment: We collected information on demographic and clinical variables by using an ad hoc questionnaire. For psychopathology, we employed the Spanish versions of the following psychometric instruments: the Positive and Negative Syndrome Scale (PANSS), the Brief Negative Symptom Scale (BNSS-Sp), and the Calgary Depression Scale (CDS). In addition, cognitive domains were assessed using the Verbal Fluency Test (VFT), the Digit Symbol Substitution Test (DSST), and the Trail Making Test, parts A and B (TMT-A and TMT-B). Finally, we employed the Spanish versions of the University of California San Diego Performance-based Skills Assessment (Sp-UPSA) and the Personal and Social Performance (PSP) for assessing functional capacity and real-world functioning, respectively. Statistical analysis: A forward stepwise regression was conducted by entering those variables significantly associated with PSP total score into the univariate analyses (Student's t-test, ANOVA with Duncan's post-hoc test, or bivariate Pearson correlation).Results: A total of 144 patients; mean age 40 years, 64% males, mean length of illness 12.4 years, PSP total score 54.3. The final model was a significant predictor of real-world functioning [F(7, 131) = 36.371, p < 0.001] and explained 66.0% of the variance. Variables retained in the model: BNSS-Sp abulia, asociality, and blunted affect, PANSS general psychopathology, Sp-UPSA transportation, TMT-B, and heart rate.Conclusion: Our model will contribute to a more efficient and personalized daily clinical practice by assigning specific interventions to each patient based on specific impaired factors in order to improve functioning.

ObjectivesThough it is known to all that PARP inhibitors (PARPis) are effective when used as maintenance alone for women with recurrent ovarian cancer (ROC), little is known about whether using them in combination with other drugs would contribute to a better efficacy. We performed a systematic review and meta-analysis to explore the efficacy and safety of PARPi combination therapy compared with monotherapy.Materials and MethodsWe searched for randomized controlled trials (RCTs) that offered the date we needed in PubMed, Embase, Cochrane, and major conference. Data extraction and processing were completed by three investigators to compare OS, PFS, and ORR both in intervention and in control subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. And we evaluated the within-study heterogeneity by using subgroup and sensitivity analysis.Results and ConclusionA total of three eligible RCTs covering 343 women were included. In PFS analysis, PARP inhibitor (PARPi) combination therapy can significantly improve PFS for women with ROC when compared with the controls (HR: 0.46, 95% CI: 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45). And in OS analysis, combination therapy is not inferior to monotherapy (HR: 0.90, 95% CI: 0.50 to 1.61). As for ORR, the effectiveness of combination therapy and monotherapy was almost the same (RR: 1.04, 95% CI: 0.82 to 1.31). Additionally, combination therapy seldom causes more adverse events, both in all-grade and in high grade.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, International Prospective Register of Systematic Reviews (PROSPERO) (identifier, CRD42018109933).