First-line Therapy Research Articles

Has Coca-Cola treatment become the first-line therapy for gastric bezoars, both in general and specifically for western countries?

Has Coca-Cola treatment become the first-line therapy for gastric bezoars, both in general and specifically for western countries?

MYC family amplification dictates sensitivity to BET bromodomain protein inhibitor Mivebresib (ABBV-075) in small-cell lung cancer.

Small-cell lung cancer (SCLC) accounts for nearly 15% of all lung cancers. Although patients respond to first-line therapy readily, rapid relapse is inevitable, with few treatment options in the second-line setting. Here, we describe SCLC cell lines harboring amplification of MYC and MYCN, but not MYCL1 nor non-amplified MYC cell lines, exhibit superior sensitivity to treatment with the pan-BET bromodomain protein inhibitor Mivebresib (ABBV-075). Silencing MYC and MYCN partially rescued SCLC cell lines harboring these respective amplifications from the anti-proliferative effects of mivebresib. Further characterization of genome-wide binding of MYC, MYCN, and MYCL1 uncovered unique enhancer and epigenetic preferences. Implications: Our study suggests that chromatin landscapes could establish cell states with unique gene expression programs, conveying sensitivity to epigenetic inhibitors such as mivebresib.

MicroRNA-451 Regulates Angiogenesis in Intracerebral Hemorrhage by Targeting Macrophage Migration Inhibitory Factor.

Intracerebral hemorrhage (ICH) is a subtype of stroke with the highest fatality and disability rate. Up to now, commonly used first-line therapies have limited value in improving prognosis. Angiogenesis is essential to neurological recovery after ICH. Recent studies have shown that microRNA-451(miR-451) plays an important role in angiogenesis by regulating the function of vascular endothelial cells. We found miR-451 was significantly decreased in the peripheral blood of ICH patients in the acute stage. Based on the clinical findings, we conducted this study to investigate the potential regulatory effect of miR-451 on angiogenesis after ICH. The expression of miR-451 in ICH mouse model and in a hemin toxicity model of human brain microvascular endothelial cells (hBMECs) was decreased the same as in ICH patients. MiR-451 negatively regulated the proliferation, migration, and tube formation of hBMECs in vitro. MiR-451 negatively regulated the microvessel density in the perihematoma tissue and affected neural functional recovery of ICH mouse model. Knockdown of miR-451 could recovered tight junction and protect the integrity of blood-brain barrier after ICH. Based on bioinformatic programs, macrophage migration inhibitory factor (MIF) was predicted to be the target gene and identified to be regulated by miR-451 inhibiting the protein translation. And p-AKT and p-ERK were verified to be downstream of MIF in angiogenesis. These results all suggest that miR-451 will be a potential target for regulating angiogenesis in ICH.

Milrinone in persistent pulmonary hypertension of newborn: a scoping review.

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited. IMPACT: Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy. This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results. Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy.

Effectiveness of double-dose dolutegravir in people receiving rifampin-based tuberculosis treatment: an observational, cohort study of people with HIV from six countries.

Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50 mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV. Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment. We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000 copies/mL. In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

SPP1 expression indicates outcome of immunotherapy plus tyrosine kinase inhibition in advanced renal cell carcinoma

ABSTRACT Clinical guidelines have recently advised combination therapy involving immunotherapy (IO) and tyrosine kinase inhibitors (TKI) as the first-line therapy approach for advanced renal cell carcinoma (RCC). Nevertheless, there is currently no available biomarker that can effectively distinguish the progression-free survival (PFS). RNA-sequencing and immunohistochemistry were conducted on our cohort of metastatic RCC patients, namely ZS-MRCC, who received combination therapy consisting of IO and TKI. We further applied RNA-sequencing, immunohistochemistry, and flow cytometry to examine the immune cell infiltration and functionality inside the tumor microenvironment of high-risk localized RCC samples. SPP1 expression was significantly higher in non-responders to IO-TKI therapy. Elevated levels of SPP1 were associated with poor PFS in both the ZS-MRCC cohort (HR = 2.73, p = .018) and validated in the JAVELIN Renal 101 cohort (HR = 1.61, p = .004). By multivariate Cox analysis, SPP1 was identified as a significant independent prognosticator. Furthermore, there existed a negative correlation between elevated levels of SPP1 and the presence of GZMB+CD8+ T cells (Spearman’s ρ= −0.48, p < .001). Conversely, SPP1 expression is associated with T cell exhaustion markers. A significant increase in the abundance of Tregs was observed in tumors with high levels of SPP1. Additionally, a machine-learning-based model was constructed to predict the benefit of IO-TKI treatment. High SPP1 is associated with therapeutic resistance and unfavorable PFS in IO-TKI therapy. SPP1 expression have also been observed to be indicative of malfunction and exhaustion in T cells. Increased SPP1 expression has the potential to serve as a potential biomarker for treatment selection of metastatic RCC.

Outcome of Hairy Cell Leukemia: A Single-center Study

Abstract: BACKGROUND: Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder. Modern therapy with purine analogs and immunotherapy can provide long-term remission, but the risk of recurrence remains about 40%–50%. The aim of this study was to evaluate the outcome of patients with HCL who received treatment in Nanakali Hospital. PATIENTS AND METHODS: A retrospective cross-sectional study was carried out on 50 patients of HCL diagnosed from 2004 to 2022 in Nanakali Hospital in Erbil City, Kurdistan Region, Iraq. Demographics, clinical presentation, treatment data, complications, response, recurrence, and survival data were collected from medical records. The results were presented with descriptive statistics. Variables were compared by Chi-square analysis. RESULTS: The mean age was 52.64 ± 12.37 years, and 84% were male. The most common presenting symptoms were splenomegaly (18%) and fatigue (14%). The majority (69.6%) received cladribine; the response rate was 73.9%, with a complete remission (67.4%). 47.8% had recurrent disease. The most common adverse effects were febrile neutropenia (58.7%) and Grade III and IV hematologic toxicity (41.3%). The results were significantly associated with ANC pretreatment (P = 0.019), comorbidity (P = 0.001), and treatment response (P = 0.004). Cladribine–rituximab combination resulted in complete remission (100%). Ten-year overall survival was 70%. CONCLUSIONS: The results were broadly consistent with literature reports, demonstrating the efficacy and safety of cladribine with/without rituximab as first-line therapy for HCL but with a 30% mortality of concern. Further studies should identify modifiable factors that affect poor prognosis in subgroups to guide improvements in risk management of HCL.

Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired hepatic function, or local recurrence following surgical resection preclude operative management as the sole treatment modality in a subgroup of patients. As such, systemic therapies, namely immunotherapy, have become an integral part of the HCC treatment algorithm over the past decade. While agents, such as atezolizumab/bevacizumab, have well-established roles as first-line systemic therapy in intermediate- and advanced-stage HCC, the role of immunotherapy in disease amenable to surgical management continues to evolve. In this review, we will discuss the current evidence and aggregate impact of immunotherapy in the context of HCC amenable to surgical management, including its application in the neoadjuvant and adjuvant settings.

Pharmacokinetics and Safety of Intramuscular Injectable Benzathine Penicillin G in Japanese Healthy Participants.

An intramuscular (IM) suspension of benzathine penicillin G (BPG) has been used as first-line therapy for the treatment of syphilis worldwide since its approval in the 1950s. However, there are limited reports about the pharmacokinetics of BPG. A Phase 1 study was conducted on eight Japanese healthy participants to investigate the pharmacokinetics (samples collected predose to 648 h post-dose) and safety of 2.4 million units of BPG after a single IM injection. Following administration, penicillin G, the active moiety of BPG, was absorbed slowly from the injection site with a median time to Cmax (tmax) of 48 h post-dose. After the achievement of Cmax, concentrations of penicillin G declined slowly in a monophasic fashion with a mean apparent terminal half-life of 189 h. Geometric mean AUCinf and Cmax were 50770 ng•h/mL and 259 ng/mL, respectively. Median time (range) above the well-accepted therapeutic concentration (18 ng/mL) for syphilis treatment was 561 h (439-608 h [18-25 days]), which reached and exceeded the necessary duration of 7-10 days for syphilis treatment. Two participants were underdosed with residual drug left in the syringe due to the high viscosity of the drug product. Only one (12.5%) participant reported a mild adverse event of nasopharyngitis, which was considered not related to the study treatment. The study results supported BPG approval in Japan as an option for syphilis treatment.

Toripalimab plus cetuximab combined with radiotherapy in a locally advanced platinum-based chemotherapy-insensitive nasopharyngeal carcinoma patient: a case report

BackgroundLocoregionally advanced nasopharyngeal carcinoma (NPC) is an epithelial malignancy that primarily occurs in East and Southeast Asia, and it is associated with relatively poor overall survival (OS). Currently, there is no reliably effective standard treatment for NPC that progresses after first-line therapy with platinum-based chemotherapy.Case reportA 55-year-old woman diagnosed with stage IVa NPC received two cycles of platinum-based chemotherapy but encountered an increase in the size of cervical lymph nodes and suffered from adverse events. The patient was then switched to toripalimab plus cetuximab combined with radical radiotherapy and had a complete clinical response within 2 months following the completion of radiotherapy without severe treatment-related adverse events.ConclusionThis case report showed that toripalimab plus cetuximab combined with radiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma may result in a fast and durable response with a manageable safety profile.

Prospective open-label trial with rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy not responding to conventional immune therapies

BackgroundTo evaluate the efficacy of rituximab in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients not responding to conventional immune therapies.MethodsAn open-label, prospective exploratory study was conducted with intravenous rituximab on 17...

A cost effectiveness analysis of two treatment strategies for trigeminal neuralgia in Ontario

Background: Trigeminal neuralgia (TN) is a debilitating disease with an annual incidence of approximately 4–27/100,000. In Ontario, over 2000 patients receive interventions for profound pain, including medical and surgical therapies. The global expected cost of these approaches is unknown. This study aims to analyze the cost-effectiveness of one surgical therapy, microvascular decompression (MVD), compared with the best medical therapy (carbamazepine) as first-line therapy. Methods: Costs were gathered from the Canadian Institute for Health Information, Ontario Drug Benefit Formulary, and Ontario Ministry of Health Schedule of Benefits for Physician Services. Academic literature was used to estimate unavailable items. A cost-benefit Markov model was created for each strategy with literature-based rates for annual cycles from years 1 to 5, followed by a linear recurrent cycle from years 6 to 10. Incremental cost-effectiveness ratios (ICERs) were calculated based on the incremental cost in 2022 Canadian Dollars (CAD) per pain-free year. Results: Base case cost per patient was $10,866 at 10 years in the “MVD first” group and $10,710 in the “carbamazepine first” group. Ten-year ICER was $1,104 for “MVD first,” with strict superiority beyond this time point. One-way deterministic sensitivity analysis for multiple factors suggested the highest cost variability and ICER variability were due to surgery cost, medication failure rate, and medication cost. Conclusion: Economic benefit is established for a “MVD first” strategy in the Ontario context with strict superiority beyond the 10-year horizon. If a cost-effectiveness threshold of $50,000 per pain-controlled year is used, the benefit is established at 4 years.

Cost-effectiveness of avelumab first-line maintenance therapy for adult patients with locally advanced or metastatic urothelial carcinoma in France.

This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France. A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses. Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER. This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.

Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review

Metformin, a widely used first-line anti-diabetic therapy for the treatment of type-2 diabetes, has been shown to lower hyperglycemia levels in the blood by enhancing insulin actions. For several decades this drug has been used globally to successfully control hyperglycemia. Lactic acidosis has been shown to be a major adverse effect of metformin in some type-2 diabetic patients, but several studies suggest that it is a typically well-tolerated and safe drug in most patients. Further, recent studies also indicate its potential to reduce the symptoms associated with various inflammatory complications and infectious diseases including coronavirus disease 2019 (COVID-19). These studies suggest that besides diabetes, metformin could be used as an adjuvant drug to control inflammatory and infectious diseases. In this article, we discuss the current understanding of the role of the anti-diabetic drug metformin in the prevention of various inflammatory complications and infectious diseases in both diabetics and non-diabetics.

Results of treatment of patients with newly diagnosed immune thrombocytopenia: is it justified to follow clinical recommendations?

Immune thrombocytopenia (ITP) is an acquired immune-mediated disease characterized by isolated transient or persistent thrombocytopenia &lt; 100·109/L. The incidence of immune thrombocytopenia is 4–6,4 per 105 children/year.Purpose. To analyze the results of treatment newly diagnosed immune thrombocytopenia according to the clinical guidelines (ID699) published on the website of the Ministry of Health of Russia.Material and methods. The analysis included 13 patients (F–46%, M–54%, median age — 9.5 (4–17) years) with immune thrombocytopenia admitted to the Tver Regional children hospital in 2023. A history of infection preceding the immune thrombocytopenia was in 69% of cases and measles vaccination in 8%. The median period from the onset of infection was 11 (5–15) days. Degree of bleeding was — 1 gr. — 4 (31%), 2 gr. — 3 (23%), 3 gr. — 6 (46%). Hematuria was observed in 3 (23%), menorrhagia in 1 (8%) case. The mean platelet count at the time of admission was 9,0 (1.0–86) · 109/l.Results. The incidence was 5.7 per 105 children/year. Dexamethasone 20 mg/m2, days 1–3, was used in 54% of cases; IVIG 1000 mg/kg, day 1 in 15%, prednisolone 2 mg/kg, day 21 in 8% and in 23% of cases dynamic follow-up was performed. In 2 cases (17%), discontinuation of steroid therapy and switching to IVIG was required due to a hemorrhagic syndrome deterioration or/and complication of steroid therapy. Partial and complete responses were achieved in 8 (62%) and 4 (31%) cases respectively. In 1 (8%) case, the response could not be evaluated. The summary efficacy of first-line therapy was 92%.Conclusion. The clinical guidelines ID699 was highly effective in achieving a primary response and preventing recurrence of immune thrombocytopenia in children.

Diagnosis and treatment of dyslipidemia in children and adolescents

Background: Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality worldwide, including in South Korea. Dyslipidemia is an independent risk factor for the development of atherosclerotic cardiovascular diseases. There is strong evidence that atherosclerosis begins early in life and that elevated lipid levels in childhood predict elevated lipid levels into adulthood.Current Concepts: A universal approach for cholesterol screening in all children is recommended. Lipid profiles should be studied for all children aged 9 to 11 years and then for those aged 17 to 21 years, as cholesterol levels may vary after puberty. The non-fasting lipid profile can be as useful in detecting severe genetic dyslipidemias as the fasting lipid profile and thus can be used as a first-line screening in children. The initial treatment for dyslipidemia in a child always begins with a 6-month trial of lifestyle modifications, such as improvements in dietary and physical activity patterns. Statins are as effective in children as in adults and can lower low-density lipoprotein cholesterol levels by up to 50%. Therefore, they are considered first-line therapy for children who meet the criteria for pharmacological therapy.Discussion and Conclusion: Statins and non-statin lipid-lowering agents can lower cholesterol levels with minimal adverse effects in children and adolescents with hypercholesterolemia. However, limited data is currently available on the long-term safety and efficacy of lipid-lowering agents in the pediatric population. Furthermore, non-statin lipid-lowering agents are used far less frequently in children. Therefore, further long-term safety and efficacy studies on lipid-lowering agents in pediatric populations and clinical trials with non-statin lipid-lowering agents are required.

J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan.

The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

Nivolumab + Ipilimumab as Immunotherapeutic Boost in Metastatic Urothelial Carcinoma

Studies with nivolumab, an approved therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy, demonstrate improved outcomes with added high-dose ipilimumab. To assess efficacy and safety of a tailored approach using nivolumab + ipilimumab as an immunotherapeutic boost for mUC. In this phase 2 nonrandomized trial, patients with mUC composed 2 cohorts. Cohort 1 received first-line or second-/third-line nivolumab with escalating doses of ipilimumab, and cohort 2 received second-/third-line nivolumab with high-dose ipilimumab. Recruitment spanned 26 sites in Germany and Austria from August 8, 2017, to February 18, 2021. All patients had a 70% or higher Karnofsky Performance Score and measurable disease per Response Evaluation Criteria in Solid Tumours, version 1.1. All patients initiated 4 doses of 240-mg nivolumab (1× every 2 wk). Week 8 nonresponders received nivolumab + ipilimumab (1× every 3 wk). Cohort 1 received 2 doses of 3-mg/kg nivolumab + 1-mg/kg ipilimumab followed by 2 doses of 1-mg/kg nivolumab + 3-mg/kg ipilimumab if no response. Due to safety concerns, cohort 1 treatment was halted, and first-line cohort 2 treatment was not pursued. Cohort 2 received 2 to 4 doses of 1-mg/kg nivolumab + 3-mg/kg ipilimumab. Responders continued with nivolumab maintenance but could receive nivolumab + ipilimumab for later progression. The primary end point was objective response rate. The study comprised 169 patients (118 [69.8%] men; median [range] age, 68 [37-84] years): 86 in cohort 1 (42 first-line; 44 second-/third-line) and 83 in cohort 2. The median (IQR) follow-up times were 10.4 (4.2-23.5) months (first-line cohort 1), 7.5 (3.1-23.8) months (second-/third-line cohort 1), and 6.2 (3.2-22.7) months (cohort 2). Response rates to nivolumab induction were 12/42 (29%, first-line cohort 1), 10/44 (23%, second-/third-line cohort 1), and 17/83 (20%, cohort 2). Response rates to a tailored approach were 20/42 (48% [90% CI, 34%-61%], first-line cohort 1), 12/44 (27% [90% CI, 17%-40%], second-/third-line cohort 1), and 27/83 (33% [90% CI, 23%-42%], cohort 2). Three-year overall survival rates for first-line cohort 1, second-/third-line cohort 1, and cohort 2 using the Kaplan-Meier method were 32% (95% CI, 17%-49%), 19% (95% CI, 8%-33%), and 34% (95% CI, 23%-44%), respectively. In this nonrandomized trial, although first-line cohort 1 treatment improved objective response rates, considerable progression events urge caution with this as a first-line therapy. Second-/third-line cohort 1 treatment did not improve response rates compared with nivolumab monotherapy. However, added high-dose ipilimumab may improve tumor response and survival in patients with mUC. ClinicalTrials.gov Identifier: NCT03219775.

Severe ocular Mpox in person living with advanced HIV treated with extended course of tecovirimat.

People living with HIV are disproportionately represented among people with severe mpox. Mild and self-limiting conjunctival involvement has been well-documented, and severe ocular complications, including keratitis, corneal scarring, and the associated loss of vision, are increasingly recognized. Tecovirimat is the first-line antiviral therapy for severe mpox, but data around the efficacy of systemic antiviral agents for mpox are limited, particularly in cases of ocular mpox. Here, we describe a case of sight-threatening necrotic blepharokeratoconjunctivitis in a person with advanced HIV, requiring an extended course of tecovirimat due to persistent mpox viral shedding for nearly 5 months.

Reperfusion therapies in patients with intermediate- and high-risk pulmonary embolism: insights from a multicenter registry

Abstract Funding Acknowledgements None. Background Most acute pulmonary embolism (PE) patients receive anticoagulation as a sole treatment. Reperfusion therapies are required in high-risk (HR) and in intermediate-risk (IR)-PE patients with clinical deterioration. Systemic thrombolysis (ST) is the first-line reperfusion therapy, but due to contraindications and major bleeding concerns, catheter-directed therapies (CDT) are rising as a suitable alternative. Purpose The main objective of this study was to look for predictors that lead physicians to decide between different PE therapies in a contemporary cohort of patients. Methods This ambispective registry included consecutive IR- and HR-acute PE patients evaluated by local Pulmonary Embolism Response Team in two tertiary centers from 2014 to 2022. The patients were grouped according to the elected therapy: anticoagulation alone, CDT or ST. If more than one reperfusion therapy was used, the patient was assigned to the group of the first administered therapy. Predictors of reperfusion therapy assignment were evaluated using a logistic regression analysis. Also, early safety outcomes and procedural results after CDT were analyzed. Results A total of 274 patients were included. Of them, 112 received only anticoagulation, 96 received ST as primary treatment, and 66 underwent CDT at first. Baseline characteristics are displayed in Picture 1. Patients in the ST group were significantly younger (p&amp;lt;0.01). Comorbidities were higher in the CDT group compared to the other two. Patients undergoing CDT or ST had higher PE severity parameters at hospital admission than the anticoagulation group (e.g. shock index, RV involvement, or lactate levels; p&amp;lt;0.01 for all). The Pulmonary Embolism Severity Index score, which incorporates comorbidities and PE severity parameters, was higher in CDT patients compared to the other two groups (p&amp;lt;0.01). Picture 2 shows the trend in the choice between the two primary reperfusion therapies over the years. After multivariable analysis, the Charlson comorbidity index, recent surgery and bilateral central PE remained independent predictors for the use of CDT instead of ST (p&amp;lt;0.05 for all). A significant decrease in the systolic and mean pulmonary artery pressure and a significant increase in systolic blood pressure after procedure was detected in patients undergoing CDT. Regarding early safety outcomes, intracranial bleeding occurred only in the ST group. In contrast, the incidence of major bleeding, acute kidney injury and 30-day mortality did not differ between CDT and ST groups. Conclusion This contemporary registry used CDT as primary therapy in 24% of IHR and HR patients, mainly in comorbid and post-surgical patients, and increased over time. CDT was a safe and effective alternative to ST, achieving significant and early improvement in right ventricular function and hemodynamics.Baseline characteristicsChoice of reperfusion therapy over time