Efficacy Of Regimen Research Articles

Efficacy of neoadjuvant PD-1/PD-L1 inhibitor in resectable NSCLC: a meta-analysis based on randomized controlled trials

BackgroundThe efficacy of neoadjuvant immunotherapy in resectable non-small-cell lung cancer (NSCLC) is controversial. The aim of this study is to explore the efficacy of additional PD-1/PD-L1 inhibitors in the neoadjuvant treatment of resctable NSCLC.MethodsData sources included Cochrane Library, Embase, Web of Science, and PubMed from beginning of the database creation to May 2024. The primary outcomes of the study included event-free survival (EFS), overall survival (OS), pathological complete response (pCR), major pathological response (MPR).ResultsSeven RCTs, including 2929 patients, were included in the analysis. The results showed that the experimental group had significantly higher rates of pCR (RR = 5.9, p < 0.001) and MPR (RR = 2.88, p < 0.001) compared to the control group. OS (HR = 0.57) and EFS (HR = 0.58) was also significantly improved in the experimental group. Subgroup analysis of EFS revealed that the benefit was higher in the East (HR = 0.56) than in the West (HR = 0.70). Additionally, the benefit seemed to rise with PD-L1 tumor cell proportion score (TPS) (TPS < 1%, HR = 0.76; 1% < TPS < 49%, HR = 0.56; TPS ≥ 50%, HR = 0.38). The benefit degree seemed to be higher in the III period patients (HR = 0.75) than I-II period patients (HR = 0.52). It is important to emphasize that smokers (HR = 0.54, p < 0.001) benefited from neoadjuvant immunotherapy but nonsmokers (HR = 0.68, p = 0.055) did not.ConclusionNeoadjuvant PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the short-term and long-term prognosis of patients with resectable NSCLC. Moreover, the efficacy of this treatment regimen may be affected by different clinicopathological characteristics of patients.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model.

Chemo-free salvage treatment outperforms traditional chemotherapy in advanced lines of relapsed/refractory subcutaneous panniculitis-like T-cell lymphoma

IntroductionSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma with a good prognosis, but the optimal treatment for relapsed/refractory (R/R) SPTCL has been rarely discussed.MethodsThis study aims to compare the efficacy of conventional chemotherapy and chemo-free immunomodulatory regimen for R/R SPTCL. We retrospectively reviewed the patients with first relapse or primary refractory SPTCL between September 1997 and October 2020.ResultsA total of 19 patients with R/R SPTCL with a median age of 34 were included. All patient received the first-line chemotherapy-based treatment with a median PFS of 1.8 months. In these patients, 16 received salvage second-line treatment with an ORR of 31.3% and a median TTNT of 3.0 months. 13 of these 16 patients received chemotherapy-based treatment, resulting in a median TTNT of 2.4 months. 2 of these 16 patients received allogeneic hematopoietic stem cell transplantation and achieved long term complete remission (CR). In third-line treatment, 7 patients received chemotherapy-based regimen and 6 received chemo-free regimen such as VRMP (bortezomib, lenadomide and methylprednisolone) regimen and CsA plus IFNα regimen. The median TTNT of chemotherapy and chemo-free group were 3.2 months and not reached, respectively.DiscussionChemo-free group had a better TTNT than chemotherapy group (p=0.007). The use of chemotherapy-free regimens for R/R SPTCL appears promising and warrants further validation.

Contribution of telacebec to novel drug regimens in a murine tuberculosis model.

The clinical efficacy of combination drug regimens containing the first-generation diarylquinoline (DARQ) bedaquiline in the treatment of multidrug-resistant tuberculosis has validated ATP synthesis as a vulnerable pathway in Mycobacterium tuberculosis. New DARQs in clinical development may be even more effective than bedaquiline, including against emerging bedaquiline-resistant strains. Telacebec (T) is a novel cytochrome bc1:aa3 oxidase inhibitor that also inhibits ATP synthesis. Based on its demonstrated efficacy as a monotherapy in mice and in a phase 2a clinical trial, we tested the contribution of T to novel combination therapies against two strains of M. tuberculosis (H37Rv and HN878) in an established BALB/c mouse model of tuberculosis in an effort to find more effective regimens. Overall, T was more effective in regimens against the HN878 strain than against the H37Rv strain, a finding supported by the greater vulnerability of the former strain to T and to genetic depletion of QcrB. Against both strains, combinations of a DARQ, clofazimine, and T were highly bactericidal. However, only against HN878 did T contribute synergistically, whereas an antagonistic effect was observed against H37Rv. These results demonstrate the therapeutic potential of T and highlight how differences in the susceptibility of M. tuberculosis strains could lead to different conclusions about a drug's potential contribution to novel drug regimens.CLINICAL TRIALSThis study is registered with Clinicaltrials.gov as NCT04890535 and NCT06058299.

Treatment adherence and effectiveness in patients treated with carfilzomib-based therapy combinations for relapsed/refractory multiple myeloma in Germany: interim results from the non-interventional CARO study

Therapy adherence can significantly influence the outcome of cancer patients. The prospective, non-interventional CARO study (NCT02970747) investigated adherence, effectiveness, and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in the German real-world setting. In total, 359 patients were included at 69 sites. Data on carfilzomib combination regimens were evaluated for three treatment cohorts: carfilzomib with lenalidomide and dexamethasone (KRd), with dexamethasone only (Kd) or with daratumumab and dexamethasone (KdD). Encouragingly, patients maintained levels of treatment adherence ≥95% to carfilzomib across cohorts. The effectiveness outcomes of CARO were in line with previous data. Median PFS (95% CI) was 17.5 months (14.5, 24.7 [KRd]), 13.4 months (7.0, 18.1 [Kd]), and 15.6 months (9.9, NA [KdD]), respectively. Median OS was 38.9 months (31.5, 53.9 [KRd]), 24.2 months (17.3, 36.8 [Kd]), and not reached (KdD). Overall, the CARO study impressively demonstrates efficacy and safety of KRd, Kd, and KdD regimen in real-world.

Comparing the efficacy of a triplet antiemetic regimen in patients with esophageal cancer patients and diabetes mellitus treated with cisplatin-based chemotherapy: A retrospective study.

Cisplatin-based highly emetogenic chemotherapy is recommended in combination with neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytriptamine-3-receptor antagonist (5HT3RA), dexamethasone (DEX), and olanzapine. However, olanzapine is contraindicated in patients with pre-existing diabetes mellitus (DM). This study compared the efficacy of a triplet antiemetic regimen (NK1RA, 5HT3RA, and DEX) in patients with and without pre-existing DM treated with cisplatin-based chemotherapy. This retrospective study enrolled patients with esophageal cancer with and without pre-existing DM who received fluorouracil and cisplatin (FP) combination chemotherapy as initial therapy with a triplet antiemetic regimen for antiemetic prophylaxis. This data was compared using propensity score matching (PSM). The primary endpoint was the complete response (CR) rate during the first cycle, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120 h). The CR rate was analyzed using univariate and multivariate logistic regression, including previously reported risk factors. The significance level was set at 5%. Out of 210 eligible patients, 39 and 39 were patients with DM and non-DM patients after PSM, respectively. The CR rate measured by multivariate analysis during the overall period with DM and non-DM was 56.4% and 41.0% (adjusted odds ratio of 0.566 [95% confidence intervals: 0.209-1.536], P = 0.264), respectively. The CR rate during the delayed period (24-120 h) with DM and non-DM patients was 84.6% and 46.2% (P = 0.002), respectively. A triplet antiemetic regimen in patients with esophageal cancer with pre-existing DM might be more effective in delayed period compared to non-DM patients.

Resolution of acute motor axonal neuropathy in a patient after treatment with efgartigimod: A case report.

Guillain-Barré syndrome (GBS) is an acute autoimmune neuropathy characterized by progressive muscle weakness, often caused by immunoglobulin G (IgG) autoantibodies. There are several subtypes of GBS, of which acute motor axonal neuropathy (AMAN) is one of the most severe subtypes associated with axonal damage. It is well known that the current clinical standard of treatment is intravenous immunoglobulin (IVIg) and plasma exchange (PLEX), but some patients often show limited response or experience persistent disability. Efgartigimod, an Fc fragment of human IgG antibody, provides a way to target and reduce pathogenic IgG antibodies as a natural ligand Fc receptor (FcRn). The purpose of this study was to observe the therapeutic effect of efgartigimod on axonal GBS, which is expected to be a potential therapeutic method for GBS and AMAN. We present a case of a 58-year-old man diagnosed with AMAN, presenting with ascending symmetrical limb weakness, flaccid paralysis, and multiple cranial nerve palsies. Electromyography confirmed the axonal subtype of GBS. Despite receiving IVIg and PLEX, the patient showed suboptimal recovery. Subsequently, he was treated with efgartigimod at a dose of 10 mg/kg weekly for 4 weeks, demonstrating significant improvement in both clinical symptoms and electromyographic findings, with good tolerability. This case highlights the potential efficacy and safety of a 4-dose efgart-igimod regimen in AMAN, particularly for patients with inadequate response to conventional therapies. By targeting FcRn and promoting IgG degradation, efgartigimod offers a novel mechanism to modulate the aberrant immune response underlying AMAN. Efgartigimod at a dose of 10 mg/kg weekly for 4 weeks demonstrated promising results in this case of AMAN. While further research is warranted, our findings suggest that efgartigimod may represent a valuable addition to the therapeutic armamentarium for AMAN and potentially other autoimmune neurological conditions. Well-designed clinical trials are crucial to confirm these findings and establish optimal treatment protocols for efgartigimod in AMAN.

P14 A multicentre, randomized, double-blind, placebo-controlled Phase II study to evaluate the efficacy and safety of individual dose regimens of HB0017 in patients with moderate-to-severe plaque psoriasis

Abstract HB0017 is a recombinant humanized IgG1 monoclonal antibody that targets IL-17A. To investigate HB0017 optimal dosage and possible dosing interval during maintenance therapy to inform Phase III studies. A total of 81 patients with moderate-to-severe plaque psoriasis received HB0017 300 mg (n = 41) or placebo (n = 40) at Weeks 0, 1, 2, 4, and 8. From Week 12 to Week 28, patients in the HB0017 group were given HB0017 300 mg once every 8 weeks. And patients in the placebo group were given HB0017 300 mg at Week 12, 13, 14 and 16, and then every 4 weeks until Week 28. Efficacy, safety, pharmacokinetics, and immunogenicity were assessed in Week 36. After 12 weeks of treatment, HB0017 300 mg resulted in significantly higher PASI 90 and sPGA0/1 response rates vs. placebo (P &amp;lt; 0.001). At Week 12, in the HB0017 group, 69.4% of patients achieved PASI 90, increasing to 97.6% at Week 24, then maintained throughout the follow-up period. And 78.2% of patients achieved sPGA0/1, increased to comparable peak levels at Week 28(97.6%), then maintained to Week 36(97.5%). In the placebo group, 1.0% of patients achieved PASI 90 at Week 12, increased to 94.3% at Week 28, then maintained throughout the follow-up period. 1.1% of patients achieved sPGA0/1, increased to 91.2% at Week 24, then maintained to Week 36(91.4%). The overall safety profile of HB0017 was similar to those of similar drugs, and no new safety signals were identified. These data provide evidence to support the evaluation of HB0017 300 mg maintenance dosing both every 8 and every 4 weeks in Phase III clinical trials.

Multiorgan-on-a-chip for cancer drug pharmacokinetics-pharmacodynamics (PK-PD) modeling and simulations.

Cancer is one of the most common and fatal diseases worldwide and kills millions of people every year. Cancer drug resistance, lack of efficacy, and safety are significant problems in cancer patients. A multiorgan-on-a-chip (MOC) device consisting of breast and liver compartments was designed with AutoCAD software. The MOC molds were printed by a Formlabs Form 2 3D printer. MDA-MB-231, HepG2, and MCF-10A cells were used for the MOC experiments. The cell lines were cultured at 37°C with 5% CO2, and cell viability was assessed via Alamar blue dye to generate pharmacodynamics (PD) data. Drug concentrations from the cell culture media were analyzed via Agilent 1260 Infinity II HPLC with a Waters Symmetry C18 column and used to generate pharmacokinetics (PK) data. The PK and PD data were modeled and simulated by Monolix and Simulix software, respectively. The safety and efficacy of drug dosing regimens were compared, and the best dosing regimens were selected. This research designed and fabricated a unique MOC consisting of liver and breast compartments that overcomes the need for sealing or assembling. It was used for PK-PD modeling and simulations, and its functionality was proven experimentally. The new MOC will be helpful in preclinical trials to evaluate the efficacy and safety of drugs.

Efficacy of fosfomycin-containing regimens in treating severe infections caused by KPC-producing Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii in critically ill patients

IntroductionFosfomycin (FOS) is gaining increasing importance as part of combination therapy for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) and KPC-producing Klebsiella pneumoniae (KPC-Kp) thanks to its in-vitro synergism with several antibiotics, high tissue distribution and good tolerability.We analyzed the effect on 30-day survival of FOS-containing regimens compared to NO-FOS in critically ill patients admitted to intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication of FOS versus NO-FOS group. Materials/methodsMonocentric retrospective observational study including SARS-Cov2-negative critically ill patients with KPC-Kp or CRAB infection treated with combination antibiotic therapy with or without FOS for ≥48h (FOS vs NO-FOS groups). Primary outcome was 30-d mortality, secondary outcomes clinical cure and microbiological eradication. ResultsOf the 78 patients analyzed, 26 (33.3%) were men, median (IQR) age and Charlson Comorbidity Index (CCI) were 67 years (53-74) and 4 (2-5), respectively. Septic shock was present in 18 patients (23.1%), 37 (47.4%) were CRAB, 41 (52.6%) KPC-Kp. Compared to NO-FOS, patients receiving FOS had higher clinical cure (89.2%vs65.9%, p=0.017), early (<72h) improvement (78.4%vs52.2%, p=0.018), microbiological eradication (87.5%vs62.2%, p=0.027) and lower 7-, 14- and 30-d mortality (0%vs4.6%, p=0.027, 2.7%vs22%, p=0.016, 13.5%vs34.2%, p=0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. At multivariate analysis, receiving FOS was independently associated with survival (HR 0.29, IC95% 0.09-0.93, p=0.038), confirmed after IPTW (HR 0.501 IC95% 0.25-0.98 p=0.042). ConclusionsFOS-containing regimens exhibit higher clinical cure, higher microbiological eradication and reduced mortality than NO FOS-containing regimens in critically ill patients with CRAB and KPC-Kp infections.

Mitoxantrone-Based Novel Conditioning Regimen Leads to Great Survival Benefit in Peripheral T-Cell Lymphoma Compared to BEAM Regimen.

Peripheral T-cell lymphomas (PTCL) frequently result in relapsed or refractory diseases. Upfront autologous hematopoietic stem cell transplantation (ASCT) using the BEAM (carmustine, etoposide, cytarabine, and melphalan) regimen is recommended. However, relapses are common in PTCL, highlighting a critical need for improved survival outcomes in these patients. Anthracycline drugs are essential in treating PTCL. We compared the efficacy and tolerability of a high-dose mitoxantrone-based conditioning regimen [mitoxantrone, cyclophosphamide, and etoposide (MCE)] to the BEAM regimen in upfront ASCT for newly diagnosed PTCL patients who achieved complete or partial remission after induction therapy. A retrospective study was conducted to analyze the treatment response, progression-free survival (PFS), overall survival (OS), hematologic engraftment time, and adverse events of 64 patients between two regimens, who achieved complete or partial remission after induction chemotherapy. Twenty-eight patients received the MCE regimen, while 36 patients were treated with the BEAM regimen. There were no significant differences in clinical characteristics or the incidence of adverse events between the two groups. However, the median OS significantly favored the MCE group at 102.4 (95% CI, 87.0-117.8) months compared to 62.6 (95% CI, 50.8-74.5) months in the BEAM group (p = 0.023). Similarly, the median PFS was longer in the MCE group at 87.8 (95% CI, 65.8-109.8) months versus 42.5 (95% CI, 30.0-55.0) months in the BEAM group (p = 0.031). ASCT with the mitoxantrone-based conditioning regimen is tolerable and appears to significantly improve the prognosis of PTCL patients, offering a promising alternative to the current standard of care.

Efficacy and safety profile of 2nd line Anti TB drugs in DRTB patients in a tertiary care hospital of South Punjab.

The objective of the study was to assess the efficacy and safety profile of 2nd line Anti TB drugs in DR TB patients in a tertiary care hospital of South Punjab. This retrospective cohort study included patients who received therapy for multidrug-resistant tuberculosis (MDR-TB) between March 2018 and June 2021 at the Pulmonology Department of Sheikh Zayed Hospital, Rahim Yar Khan. Sociodemographic data, TB treatment history, treatment schemes, safety profiles, weight measures, and sputum smear results were obtained from medical records. Outcome variables of interest included body weight, sputum smear grading for treatment efficacy, and ADRs for safety assessment. The study showed a progressive decline in positive sputum smear results over the 24-month treatment for MDR-TB, with an increase in negative smear results from 33 (9.50%) at baseline to 97 (28.0%) by Month 24. Furthermore, the mean body weight significantly increased every three months throughout the trial. Beginning at 43.83 kg at baseline, the mean weight increased to 50.02 kg by the end of 24 months. ADRs were mostly mild to moderate, including depression (18.4%), arthralgia (17.1%), anxiety (16.5%), and Qtc prolongation (11.0%). The treatment adhered to international guidelines, using a tailored combination of second-line drugs and adjusting regimens based on drug resistance patterns from sputum culture and DST. The study findings suggest the efficacy of second-line anti-TB drug regimens in achieving sputum smear conversion and positive treatment outcomes in patients with MDR-TB. However, the occurrence of ADRs highlights the need for careful monitoring and management during treatment.

Strategies to Enhance Diagnostic Capabilities for the New Drug-Resistant Tuberculosis (DR-TB) Drugs

The global burden of drug-resistant tuberculosis (DR-TB) continues to challenge healthcare systems worldwide. There is a critical need to tackle DR-TB by enhancing diagnostics and drug susceptibility testing (DST) capabilities, particularly for emerging DR-TB drugs. This endeavor is crucial to optimize the efficacy of new therapeutic regimens and prevent the resistance and overuse of these invaluable weapons. Despite this urgency, there remains a lack of comprehensive review of public health measures aimed at improving the diagnostics and DST capabilities. In this review, we outline strategies to enhance the capabilities, especially tailored to address the challenges posed by resistance to new DR-TB drugs. We discuss the current landscape of DR-TB drugs, existing diagnostic and susceptibility testing methods, and notable gaps and challenges in these methods and explore strategies for ensuring fair access to DST while narrowing these disparities. The strategies include public health interventions aimed at strengthening laboratory infrastructure, workforce training, and quality assurance programs, technology transfer initiatives, involving drug developers in the DST development, establishing national or regional referral hubs, fostering collaboration and resources pooling with other infection control efforts, extending testing access in underserved areas through public–private partnerships, advocating for lowering costs or loans at low interest, remote technical support, and implementing mandatory molecular surveillance monitoring. This review underscores the urgent need to enhance DST capacities for new DR-TB drugs and identifies opportunities for innovation and improvement. Assessing the extent of the global health impact of these measures is crucial to ensure their effectiveness in combating DR-TB.

Induction chemotherapy for locally advanced nasopharyngeal carcinoma: Efficacy and safety of the TPC regimen compared to GP and TPF

Background and objectivesGemcitabine plus cisplatin (GP) and docetaxel plus cisplatin plus fluorouracil (TPF) are induction chemotherapy (IC) regimens for locally advanced nasopharyngeal carcinoma (LA-NPC). The oral convenience of capecitabine presents its potential as a fluorouracil substitute in the TPF regimen, which has yet to be thoroughly investigated. This study aims to compare the efficacy and safety of the docetaxel, cisplatin, and capecitabine (TPC) with GP and TPF in LA-NPC. MethodsA retrospective analysis was conducted on newly diagnosed stage III-IVa nasopharyngeal carcinoma patients who received GP, TPC, or TPF induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) between February 2019 and December 2021. A comparison of the prognostic outcomes and associated adverse reactions among patients receiving different IC regimens. Multivariate Cox regression was applied to analyze independent prognostic factors, and subgroup survival analyses were conducted based on these factors. ResultsA total of 291 LA-NPC patients were included, with 70 receiving TPC, 119 receiving GP, and 102 receiving TPF. Kaplan-Meier survival analysis indicated no significant differences in OS, PFS, LRFS, and DMFS among the 3 groups. Multivariate Cox regression identified T classification and clinical stage as independent prognostic factors. Subgroup analyses revealed no significant differences in OS and PFS between the 3 groups across T1-2 and T3-4 classifications or III and IVa stages.The TPC group exhibited lower incidence rates of treatment-related acute toxicity reactions, including grade 3–4 toxicities. ConclusionThe TPC induction chemotherapy regimen demonstrates comparable efficacy to GP and TPF, while maintaining a favorable safety profile.

Outcomes after a virological failure to first-line second-generation INSTI-based therapy in a real-life setting.

Virological failures of first-line second-generation (SG) INSTI-based regimens are rare, usually characterized by low viremia and absence of drug resistance mutations. To explore the efficacy of rescue regimens introduced after virological failure (VF) to a first-line SG-INSTI therapy. This was a retrospective study on people living with HIV (PWH) failing a first-line SG-INSTI regimen [DTG/3TC, BIC/FTC/TAF, DTG-based three-drug regimen (DTG-3DR)] between 24 March 2016 and 31 December 2021. Follow-up accrued from the second viral load (VL) ≥ 50 copies/mL under SG-INSTI regimen (baseline) until virological success (VS, achievement of at least one VL < 50 copies/mL after baseline) or last visit. Cumulative probabilities of VS were estimated by Kaplan-Meier curves and compared using a log-rank test. Overall, of 521 naïve PWH who started a first-line SG-INSTI regimen, 45 (8.6%) had VF after a median of 14.9 (IQR = 6.9-25.9) months: 33/395 (8.4%) individuals failed a DTG-3DR, 11/102 (10.8%) a BIC/FTC/TAF and 1/24 (4.2%) failed a DTG/3TC.At baseline, 12/45 (27%) PWH changed antiretroviral therapy [median baseline VL 134 (IQR = 81-233) copies/mL], while 33 (73%) maintained their failing regimen [median baseline VL 75 (IQR = 60-145) copies/mL].During a median follow-up of 5.13 (IQR = 3.8-7.1) months, 34 (75.6%) PWH achieved VS: 25/33 (75.8%) maintaining their failing regimen, 9/12 (75%) switched regimen; the estimated 6- and 12-months probabilities of VS were 59% and 84%, respectively.There was no difference in VS curves between PWH who maintained their failing regimen and those who switched therapy. Most individuals remained on their failing regimen, achieving spontaneous virological suppression in most cases. These data help to understand a real-life VF scenario in the context of the current SG-INSTI era.

Tailoring cell therapies for diabetic metabolic phenotypes: a comparative study on the efficacy of various umbilical cord-derived cell regimens.

Given the high heterogeneity of type 2 diabetes mellitus (T2DM), it is imperative to develop personalized stem cell infusion regimen for targeted metabolic phenotype in order to ensure optimal therapeutic efficacy. In this study, we conducted a comparative analysis of 4 infusion regimens involving single and repeated infusions of human umbilical cord Wharton's jelly-derived MSCs (hucMSCs), single infusions of umbilical cord blood mononuclear cells (UCB), and sequential infusions of hucMSCs and UCB in T2DM rats. Results showed all 4 infusion regimens exhibited comparable efficacy in lowering fasting blood glucose levels and suppressing glucagon secretion. Single and double infusions of hucMSCs exhibited a tendency to migrate to the liver, thereby better at ameliorating hepatic glucose metabolism by enhancing glycogen synthesis and storage, promoting glycolysis, inhibiting gluconeogenesis, and improving insulin signal transduction. The sequential infusion of hucMSCs and UCB demonstrated specific cell tropism toward the pancreas, leading to prolonged glucose-lowering effects following a glucose tolerance test, restoration of early-phase insulin secretion, stimulation of islet beta cell proliferation and improvement in the beta/alpha ratio. Multiple injections, regardless of cell type, reduced the expression of systemic chronic inflammatory markers such as IL-1β, IL-6, IL-17, IL-22, and IFN-γ. Finally, a single dose of UCB exhibited a greater tendency to target visceral fat and enhanced effectiveness in regulating levels of total cholesterol and triglycerides. In conclusion, our study provided personalized stem cell regimens for diverse T2DM metabolic phenotypes, thereby offering improved treatment alternatives for future clinical trials and applications.

Efficacy of Terpinen-4-ol Combined With Eyelid Deep Cleaning for the Treatment of Demodex Blepharitis: A Randomized, Open-Label Trial.

We aimed to evaluate the clinical efficacy of a combined treatment regimen involving terpinen-4-ol (T4O) and eyelid deep cleaning for managing Demodex blepharitis. In this randomized, open-label trial, 40 patients diagnosed with Demodex blepharitis at the Cornea Specialty Clinic of Hankou Aier Eye Hospital were enrolled. Participants were randomly assigned to either a T4O or a combination treatment group. The T4O group used T4O cleaning wipes exclusively for two months. The combination group used T4O cleaning wipes and underwent deep eyelid cleaning at three scheduled visits (initial, first-, and second-month time points). A final follow-up was conducted one month after completion of treatment (three months after the beginning of treatment). At each visit, we assessed the number of Demodex mites, the ocular surface disease index (OSDI), eyelid margin sign scores, and corneal fluorescein staining scores. After two months of treatment, both the T4O and combination groups exhibited significant reductions in Demodex mite counts of 5.65 ± 6.03 and 7.75 ± 6.91, respectively. The T4O group, however, showed an increase in mite counts one month after ceasing treatment. Conversely, the combination group maintained and enhanced the reduction in mite counts post-treatment, with a significant difference at the third-month follow-up (8.70 ± 6.81 vs. 4.15 ± 6.91, P = 0.043). Although both groups demonstrated overall declines in OSDI scores post-treatment, only the combination group showed significant improvements at the second- and third-month follow-ups. No adverse events were reported in either group. Treatment with T4O wipes for two months significantly reduces Demodex mite counts, although there is a notable risk of mite rebound when treatment is ceased. Combining T4O wipes and eyelid deep cleaning offers a more effective reduction in Demodex mite counts and improvement in ocular symptoms compared to T4O treatment alone. The study finds that T4O combined with eyelid deep cleaning is more effective in treating Demodex blepharitis, highlighting the need for appropriate treatment duration and adjunctive therapies.

Comparative analysis of efficacy and safety between D-TACE + HAIC + lenvatinib and D-TACE + lenvatinib in the treatment of unresectable massive hepatocellular carcinoma

ObjectiveThe aim of this study was to investigate the efficacy and safety of the combined treatment regimen of D-TACE, HAIC, and Lenvatinib in patients with massive hepatocellular carcinoma, with the goal of providing a safer and more effective therapeutic strategy for individuals suffering from massive hepatocellular carcinoma.Materials and methodsA retrospective analysis was conducted using clinical data from 118 patients with unresectable massive hepatocellular carcinoma who underwent treatment at the Interventional Department of Wuhan Union Hospital between June 2018 and December 2021. Based on the treatment approach, the patients were divided into two groups: the D-TACE + HAIC + Lenvatinib group (N = 54) and the D-TACE + Lenvatinib group (N = 64). The primary study endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two groups. Additionally, the occurrence of treatment-related adverse events in both groups was considered as a secondary study endpoint.ResultsFollowing the treatment, the D-TACE + HAIC + Lenvatinib group exhibited significantly higher ORR and DCR compared to the D-TACE + Lenvatinib group (68.5% vs. 43.8%, 90.7% vs. 73.4%, P < 0.05). Moreover, the D-TACE + HAIC + Lenvatinib group demonstrated longer mPFS and mOS in comparison to the D-TACE + Lenvatinib group (8.6 months vs. 6.6 months, P = 0.005; 19.5 months vs. 14.1 months, P < 0.001). There was no statistically significant difference in the occurrence rate of common treatment-related adverse events between the TACE + HAIC + Lenvatinib group and the D-TACE + Lenvatinib group (P > 0.05).ConclusionThe combined treatment regimen of D-TACE, HAIC, and Lenvatinib demonstrated superior therapeutic efficacy and safety in managing unresectable massive hepatocellular carcinoma. This combination therapy may serve as a viable option for improving the prognosis of patients with unresectable massive hepatocellular carcinoma.

Low-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia: a systematic review and meta-analysis.

The recommended standard treatment for Pneumocystis jirovecii pneumonia (PJP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) (15-20mg/kg/d TMP). However, the standard regimen may cause a high incidence of dose-related adverse events (AEs). Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose TMP-SMX regimens (<15mg/kg/d of TMP) compared with the standard regimen in patients with PJP. We searched PubMed, Embase, and the Cochrane database for relevant articles from inception to 10 March 2024. Studies were included if they focused on PJP patients receiving a low-dose TMP-SMX regimen compared with a standard regimen. The primary outcome was mortality. We assessed study quality and performed subgroup analysis and sensitivity analysis to explore potential heterogeneity among the included studies. Seven studies were included. Overall, the low-dose regimen significantly reduced the risk of mortality (odds ratio [OR] = 0.49; 95% CI, 0.30-0.80; I 2 = 16%; P = 004). This finding was confirmed in further sensitivity and subgroup analyses. The low-dose regimen also significantly reduced total AEs (OR = 0.43; 95% CI, 0.29-0.62; I 2 = 0%; P < 0.0001), and improved the incidence of most specific AEs (ORs ranged from 0.13 to 0.89). In addition, the low-dose regimen had significantly more patients completing the initial regimen (P = 0.002), fewer patients requiring dose reductions (P = 0.04), and almost significantly fewer patients requiring a switch to a second-line regimen (P = 0.06). The limited available evidence suggests that a low-dose TMP-SMX regimen significantly reduced mortality and total AEs in PJP patients. Thus, it is one of the potentially promising therapies to PJP and more high-quality and multi-center randomized trials should be conducted in the future.

Abstract B045: The impact of smoking status on the genomic landscape of lung squamous cell carcinoma

Abstract Introduction: Molecular diagnostics have become a standard of care in determining the appropriate treatment paradigm for patients with advanced non-small cell lung cancer (NSCLC). Current guidelines indicate that histology is the most important criteria in deciding on conducting molecular testing. In lung adenocarcinoma, guidelines recommend that all patients with advanced disease undergo comprehensive molecular testing. However, the current National Comprehensive Cancer Guidelines (NCCN) suggest only consideration of molecular testing in lung squamous cell carcinoma (SCC). Despite this recommendation, numerous genomic alterations (GAs) have been observed in lung SCC including amplifications, fusions, and mutations. The list of druggable genetic alterations has been growing, now including ROS1 rearrangements, RET rearrangements, and MET alterations with associated pharmacologic therapies. This suggests a role for broader comprehensive molecular profiling in NSCLC. We sought to assess the impact of smoking status on the proportion of actionable GAs in a cohort of lung SCC patients. Methods: We retrospectively reviewed liquid biopsy reports from Guardant 360 between October 2020 and July 2023 that were obtained in the context of routine clinical care at a single institution, the City of Hope Comprehensive Cancer Center. We then obtained social history from clinical documentation. Patients were categorized based on smoking status with the following categories: non-smoker, remote smoking history (quit &amp;gt;20 years prior), or smoking history (ongoing or quit within the last 20 year). Results: 56 patients were included in the final analysis. 98% (n = 55) patients had a documented smoking history, with 24% (n=13) classified as non-smokers. In total, 96% (n = 54) patients had detectable alterations of variable significance Of the 13 patients classified as non-smokers, 62% (n=8) patients had an actionable GA detected by liquid biopsy which has a current FDA approved agent. Of targetable GAs in the non-smoking cohort, the following alterations were observed: EGFR exon 19 deletion (44% , n=4), MET exon 14 skipping mutation (22%, n=2), EGFR G719S (11%, n=1), EGFR E114K (11% n=1). Of the 8 patients with targetable alterations detected, responses by RECIST included 4 partial response, 2 stable disease, and 2 progressive disease. The objective response rate (ORR) for this group was 55.6% and the clinical benefit rate (CBR) was 77.8%. Discussion: These data help illustrate the importance of genomic testing in lung SCC, particularly in patients with a non- smoking status. Given that 62% of non-smokers harbored a mutation treated with an FDA- approved agent, up-front genomic testing is of paramount importance. For smokers, numerous alterations were also detected which have been shown to result in decreased efficacy of immunotherapy regimens. This analysis helps highlight the potential value of liquid biopsy testing in lung SCC patients with both non-smoking and smoking histories. Citation Format: Adam Rock, Sahil Garg, Ravi Salgia, Victoria Villaflor, Ramya Muddasani, Erminia Massarelli, Colby Jenkins. The impact of smoking status on the genomic landscape of lung squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B045.