First-line Treatment Research Articles

Real-world data of first-line treatment with pembrolizumab for NSCLC with high PD-L1 expression in elderly patients: a subgroup analysis of HOT/NJLCG2001.

In the first-line treatment of elderly patients with advanced-stage non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score≥50%), this study aimed to determine whether pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum-based chemotherapy (COMB) should be selected. We performed a retrospective multicenter study (sub-analysis of the HOT/NJLCG2001 trial) of 299 patients with NSCLC with high PD-L1 expression who received MONO or COMB as the first-line treatment between December 2018 and January 2020. We selected patients aged 75years and older and assessed the clinical efficacy and toxicity. In total, 81 (median age: 79years) and 19 (median age: 76years) patients received MONO and COMB, respectively. Twenty patients with a performance status (PS) score of 2-3 were enrolled in the MONO group. The median progression-free survival (PFS) was 7.8 and 8.9months in the MONO and COMB groups, respectively. The median overall survival (OS) was 14.6 and 20.3months, and the 2-year survival rates were 38.8 and 49.9%, respectively. Furthermore, 29.6% and 26.3% of patients discontinued treatment due to adverse events, respectively. In MONO, patients with PS 0-1 had a longer PFS (10.5months) and OS (21.7months) than those with PS 2-3 (0.7 and 1.6months, respectively). Some elderly patients with NSCLC and high PD-L1 expression might benefit from COMB; however, MONO is considered the preferred treatment. MONO may not be an effective or feasible treatment for patients with PS 2-3, even with high PD-L1 expression.

South African occupational therapists' orthotic management of trigger finger and factors influencing their decision regarding splinting type

Background: Orthotic management of trigger finger refers to the use of splints to immobilise affected joints. The prevalence of trigger finger and the management and treatment practices utilised by occupational therapists for this affliction in South Africa, are not yet documented. Aim: To explore occupational therapists' orthotic management for clients with trigger finger in KwaZulu-Natal, and the factors influencing the therapists' decisions when prescribing orthoses. Methods: A quantitative cross-sectional study design was implemented with a sample size of 102 via a stratified random sampling approach. A survey questionnaire was administered. Data were coded using frequencies and then descriptively analysed using SPSS. Results: Findings indicated that trigger finger is common in clinical settings and the majority (99%) of the occupational therapists use splints when managing trigger finger and as a first line of treatment (69.9%). The joint-blocking splint is preferred by 96.6% of the participants with the MCP joint-blocking splint being favoured by 55.0%. The most considered factors when deciding on the splint type are clinical presentation (99.1%) and the client's occupation (92.4%), and the most preferred measures of the effectiveness of treatment are pain (97.1%) and range of motion (97%). Conclusion: The study has demonstrated that the inconsistencies noted in global research also apply in KwaZulu-Natal. Therefore, further investigation on the effectiveness of splinting and a guide on deciding on splint type as well as appropriate outcome measures, are necessary to ensure that cclients receive optimal care through evidence-informed practice. Implications for Practice: This study informs further understanding of the current assessment ptior to splinting and treatment practices that occupational therapist in the South African context provide for their clients with trigger-finger. The study demonstrates that irrespective of the participant's level of experience and their clinical settings, the considerations when deciding on splint types remain the same. The results are consistent with available literature, particularly with which splint type to use. However, the development for a guide regarding the orthotic management of trigger finger covering aspects like the splint regime and the recommendations of exercises is vital, as discrepancies emerged largely fro these areas. The type of exercises, stages at which they may be introduced, duration and requenccy should be considered for deeper engagement. the development of this protocol will ensure consistency of treatment and evidence-informed practice.

Cognitive behavioral therapy for pediatric obsessive-compulsive disorder delivered via internet videoconferencing: a manualized sensor-assisted feasibility approach

BackgroundBetween 1 and 4% of children and adolescents suffer from obsessive-compulsive disorder (OCD) worldwide, but the majority of these young people do not have access to cognitive behavioral therapy (CBT) as a first-line treatment. CBT delivered via online videoconferencing (vCBT) offers a new way to provide young people with therapy, especially in the home environment where symptoms usually occur.MethodsIn this study, we investigated the feasibility of a newly revised vCBT manual, symptom change during treatment, and effects on family life and social functioning. 20 patients with OCD, aged 12–18 years, were treated during 14 weekly sessions while using a multimodal sensor system that assessed their physiological and behavioral responses during therapy. Treatment was delivered in real time via an online videoconferencing platform. Measurements of feasibility, acceptance, and implementation were evaluated descriptively, and clinical measures were assessed with t tests.ResultsThe primary results showed that patients and parents perceived the manual-based vCBT as feasible and easy to understand. According to the therapists’ ratings, all treatment modules and the content could be carried out in accordance with the manual. As a secondary outcome, OCD symptoms improved significantly during treatment (p <.001, d = 1.87), revealed by an average decrease of more than half in the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score. As the psychotherapy could be implemented directly in the patients’ home environment, low barriers to participation were reported, and the majority of participants reported improvements in family life after treatment.ConclusionsIn summary, the results of this feasibility study indicated a successful application of manual-based psychotherapy delivered via videoconferencing for pediatric OCD supported by a sensor system. This method should be further investigated in future randomized controlled trials with larger patient samples.Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT05291611], first submission: 2021-12-10.

Safety and effectiveness of preoperative stenting compared to non-stenting in ureteroscopy for urinary stone disease: a meta-analysis of comparative studies.

Ureteroscopy (URS) is considered one of the first-line surgical treatments for urinary stones < 2cm. Preoperative stenting (PS) employment in URS for urolithiasis remains debated, with evidence differing in terms of outcomes and recommendations. We sought to evaluate the influence of PS on surgical outcomes compared to non-PS (NPS) in patients with renal and ureteral stones undergoing ureteroscopic lithotripsy. Databases were searched until December 2023 for randomized and non-randomized studies reporting perioperative outcomes for PS and NPS. Pooled data were analyzed through a Random-Effects model when Higgins I2% heterogeneity values were > 50%; otherwise, a Fixed-Effects model was employed. Results were reported as risk ratios (RR), or mean differences (MD) with 95% confidence intervals (CI). Statistical significance was set at p < 0.05. The analysis included 23,668 patients from 25 included studies (5 non-randomized prospective and 20 retrospective studies). Higher stone-free rates (SFR) were observed in kidney and ureteral stones (RR 1.05; 95%CI 1.03-1.08; p ≤ 0.0001), especially if managed with flexible URS (RR 1.05; 95%CI 1.01-1.09) in the PS cohort. Additionally, lower rates of intraoperative (RR 0.70; 95%CI 0.49-0.99; p = 0.04) and postoperative complications (RR 0.82; 95%CI 0.70-0.95; p = 0.008) were seen with PS. Both groups had a comparable operative time, length of stay (LOS), ureteral access sheath (UAS) placement success, and SFR in semi-rigid URS. Higher SFR with PS were seen in kidney and ureteral stones, especially if f-URS was employed. Moreover, perioperative complications did not increase with PS. Future randomized studies, evaluating cost-effectiveness and quality of life are needed.

A self-guided e-learning program improves metamemory outcomes in healthy older adults: a randomized controlled trial

Objectives Aging brings memory changes that can be concerning for some older adults. Whereas in-person memory interventions can positively impact knowledge, mental health, and behavioural outcomes, self-guided e-learning programs may offer scalable and accessible alternatives to in-person programming. The current study aimed to evaluate efficacy of an e-learning program compared to no treatment. Method The trial was registered at ClinicalTrials.gov (NCT03602768). As part of a larger, multi-arm, controlled trial, healthy older adults (ages 60-84, 71% female) were randomized into an intervention or a delayed-start control condition. Data collection personnel were masked to participant grouping. Outcome measures were completed through telephone interviews and online questionnaires at baseline, immediate post-intervention, and 6- to 8-week follow-up. Results Among 115 analyzed participants, there were larger improvements over time in memory knowledge, memory strategy acquisition and daily use, and self-reported memory satisfaction and ability in the group that completed the intervention than in the control group. There was no interaction effect for health-promoting behaviors. Intention-to-treat analyses showed attenuated but largely similar findings. Conclusion This self-guided e-learning memory program demonstrated similar clinical outcomes provided by in-person, facilitator-led programs. It may serve as an effective first-line treatment for older adults presenting with memory concerns in clinical settings.

Cluster headache and galcanezumab: the first real-world Brazilian study and an expert consensus on its use among other treatments

ObjectiveTo present the first Brazilian real-world results with galcanezumab and provide a consensus expert opinion on the prophylactic treatment of cluster headache (CH) in Brazil.MethodsThe first part of the study (real-world results) was observational, prospective, uncontrolled, and descriptive. A sample of 44 consecutive patients with episodic or chronic CH were evaluated and treated in a traditional tertiary clinic from March 2020 to June 2024. The second part (consensus expert opinion) consisted of a survey completed by ten Brazilian headache clinicians with at least 25 years of clinical experience, who published at least 15 headache papers and attended at least 15 national or international headache conferences.ResultsForty-four patients (86.4% men, 13.6% women) were included. The average age was 45.9 ± 14.2 years. The diagnosis was made 27.3 ± 13.6 years after the onset of headache bouts. In 84.1% of the patients, CH was classified as episodic. Verapamil, lithium, or verapamil plus lithium were prescribed to respectively, 25%, 9.1%, and 6.8% of patients. Galcanezumab was prescribed to all and the majority (65.9%) used a dose of 300 mg once. There was a reduction in headache frequency of ≥ 50% at 3 weeks in 65.9% of patients for all doses of galcanezumab, and in 72.4% of those using galcanezumab 300 mg. Verapamil was recommended as a first-line treatment by 6 of 10 experts and a second-line treatment by the other 4 experts; galcanezumab was recommended as a first-line treatment by 4 of 10 experts and as a second-line treatment by 3 of 10 experts.ConclusionsThis study presented the first real-world data with galcanezumab in Brazilian patients with CH and showed a reduction in headache frequency in most patients. A survey of Brazilian experts not meant to represent the country’s guidelines, favored galcanezumab as either the first or the second option in prophylaxis. Collectively, these results highlighted galcanezumab’s promising efficacy as a new tool in CH patients.

A review on recent advances in the stability study of anti-mycobacterial drugs.

Several factors, including characteristic polymer composition of the cell wall, based on peptidoglycans cross-linked with arabinogalactans, together with the lipid layer contribute to the high resistance of Mycobacterium tuberculosis to antibiotics and other anti-tuberculosis drugs, leading to the development of new treatment methods. Implementation of therapeutic drug monitoring for anti-mycobacterial drugs in routine clinical practice requires understanding of the limited stability of these drugs. Rifampicin and isoniazid are the main anti-tuberculosis drugs that generate degradation products during sample handling and storage. Therefore, analytical methods used for analysis of clinical samples collected from tuberculosis patients treated with a combination of different drugs should enable the separation of the studied analytes from their metabolites and degradation products. Moreover, the samples require strictly regulated collection and storage conditions to prevent degradation processes. The purpose of this review was to present recent data on the stability studies of anti-mycobacterial drugs, specifically used as first-line treatment in patients with tuberculosis. Detailed degradation pathway of rifampicin was described, including conditions influencing the formation of specific rifampicin related substances. Moreover, the results of the stability studies of anti-mycobacterial drugs were presented in various matrices in conditions determined by international guidance such as U.S. Food and Drug Administration (FDA) or International Council for Harmonisation (ICH) guidelines. Particular attention was given to analytical methods designed for analysis of anti-mycobacterial drugs in the presence of their degradation products. Finally, recommendations proposed by different authors for collection, processing and storage of clinical samples to increase stability of anti-mycobacterial drugs were summarized.

A Possible Tool for Guiding Therapeutic Approaches to Urinary Infections with Klebsiella pneumoniae: Analyzing a Dataset from a Romanian Tertiary Hospital.

Introduction: The emergence of carbapenem-resistant pathogenic bacteria is a growing global public health concern. Carbapenem-resistant uropathogenic strains of Klebsiella pneumoniae can cause uncomplicated or complicated urinary tract infections, leading to a high risk of treatment failure and the spread of resistance determinants. The objectives of this 24-month study were to identify the prognostic characteristics of patients who were infected with carbapenem-resistant Klebsiella pneumoniae (CRKpn) and to create a tool to estimate the probability of a CRKpn infection before having the complete results of a patient's antibiogram. Results: We found that 41.6% of all urinary infections with Kpn were caused by CRKpn. Factors such as male gender, the presence of upper urinary tract infections, invasive urinary maneuvers, recent infection with or carriage of the germ, and the nosocomial occurrence of UTIs with Kpn were predictive for CRKpn infection. Based on these factors, we proposed a model to estimate the presence of CRKpn. Methods: A retrospective case-control study including all hospitalized patients with urinary tract infections (UTIs) caused by Klebsiella pneumoniae was carried out. We reported data as percentages, identified independent predictors of the presence of CRKpn, and proposed a tool to evaluate the probability through multivariate analysis. Conclusions: Through this study, we aim to provide clinicians with a tool to support decision making regarding first-line antibiotic treatment.

Dry eye syndrome associated with meibomian gland dysfunction in the context of isotretinoin use: a clinical case

Introduction. Acne is a chronic, recurrent, and inflammatory skin disease that that can have significant aesthetic and psychological impacts on patients. The first-line treatment for acne is isotretinoin, which exerts systemic effect, reducing sebum production and alleviating inflammation However, one of the most common complications associated with prolonged systemic retinoid use is dry eye syndrome, linked to meibomian gland dysfunction, warranting special attention from ophthalmologists. Purpose: to present a clinical case of a patient who underwent four months of systemic isotretinoin therapy for acne and subsequently developed ocular complaints. Methods. Comprehensive ophthalmological diagnostics were conducted, including patient history, biomicroscopy, and corneal staining with fluorescein. Additional assessment included non-invasive tear film breakup time, measurement of tear meniscus height, evaluation of the lipid layer thickness of the tear film, meibography, eyelid margin photography, conjunctival hyperemia analysis, and corneal fluorescein staining. Treatment included various groups drug classes such as moisturizing drops, reparative gels, corneal protectors, and glucocorticosteroids. A therapeutic eyelid massage was also performed. Results. After three months of active therapy, the patient exhibited significant improvement, with a marked reduction in subjective complaints, no corneal epithelial defects, and an increase in tear film breakup time. Long-term symptom remission was achieved after five months of therapy. Conclusion. This case highlights the importance of interdisciplinary collaboration between ophthalmologists and dermatologists in managing patients undergoing long-term systemic retinoid therapy for acne. Comprehensive ophthal- mological assessment using specialized diagnostic methods is essential for accurately evaluating the clinical picture of ocular conditions and administering timely, multi-faceted therapy. This approach enhances patients’ quality of life and helps prevent severe complications.

Treatment of elderly patients with acute myeloid leukemia: personal experience

Background. Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic system. Most patients with newly diagnosed AML are 65 years of age or older. Treatment of this cohort of patients is difficult due to the comorbidity of elderly patients and the genetic characteristics of hemoblastosis, which prevents the achievement of significant progress in treatment, in contrast to younger patients with AML. As domestic and foreign studies have shown, age is an independent universal prognosis factor for AML. In the era of targeted drugs, successful treatment of AML is becoming possible.Aim. To assess overall survival in elderly patients with AML, tolerability and effectiveness of various treatment regimens in patients with AML ≥65 years.Materials and methods. This paper presents our own experience in the treatment of elderly patients with AML in the hematology departments of the City Clinical Hospital No. 52. The study included patients over 65 years of age with AML from April 2022 to September 2023. A total of 40 patients were analyzed. To determine the risk factors for death, univariate and multivariate regression analyzes were performed using the logistic regression method. Variables that showed statistical significance on univariate analysis were included in the multivariate analysis. An analysis of 12‑month overall survival was also carried out using the Kaplan–Meier method with the construction of survival curves and calculation of median survival. A comparative analysis of two groups of patients treated with the AZA + EN and LdaraC regimens was carried out.Results. 63 % (n = 25) are men, 37 % (n = 15) are women. The median age was 75 years; all patients had complicated premorbid background. 53 % (n = 21) of patients were in the age range from 65 to 69 years, 47 % (n = 19) were over 70. Antitumor treatment was received by 88 % (n = 35) of patients. The remaining 5 underwent: best accompanying (n = 2), cytoreductive (early death at this stage) (n = 3) therapy. Complete remission after two cycles of therapy was achieved in 46 % (n = 16) of patients, and in 29 % (n = 10) it was maintained at the time of analysis. Early relapse occurred in 14 % (n = 5). Early mortality was recorded in 9 % (n = 3). Death was reported in 40 % (n = 16) of patients. 20 % (n = 7) of patients were refractory to first-line therapy, of which 36 % (n = 5) were treated with low doses of cytarabine (LdaraC), the rest to a combination of azacitidine (AZA) with venetoclax (EN). The number of relapses among patients on AZA + EN and LdaraC therapy was comparable.Conclusion. AZA + EN is the first-line treatment of choice in older patients with AML. The possibility of conducting this course in an outpatient setting makes it most convenient for both hematologists and patients. An important aspect in the treatment of AML in elderly patients is improving and maintaining quality of life.

Glucocorticoid treatment for primary and secondary central nervous system vasculitis

Although the first-line treatment of central nervous system vasculitis (CNSV) is glucocorticoids (GC), the duration and dose of GC is still unknown. Although CNSVs seem to be a disease limited to a single area, they are a heterogeneous group of diseases clinically, in terms of involvement pattern and course. Due to the highly heterogeneous nature of the disease, patient-specific determination of the initial dose of GC is essential. Considering the disease courses, it may be more appropriate to consider 1mg/kg oral GC treatment if small/distal vessels are involved and intravenous bolus GC treatment if large/proximal vessels are involved in primary-CNSVs. In secondary-CNSVs (Anca-associated vasculitis, Behçet’s syndrome, Systemic Lupus Erythematosus) intravenous high dose GC treatment is recommended.

Heel Pain After Landing in a Soccer Player: A Case of Abductor Hallucis Strain

BACKGROUND: Plantar heel pain is often attributed to the plantar fascia and calcaneal fat pad, both for athletes and sedentary individuals. Another potential cause of heel pain is Abductor Hallucis muscle (AbdH) strain. CASE PRESENTATION: The athlete jumped for a header during a league game, and after he landed on his left foot with a dorsiflexed ankle, he felt sudden pain and was not able to continue. The initial physical examination has overlapping features of AbdH and plantar fascia injury. Detailed physical examinations and radiological images revealed AbdH strain. OUTCOME AND FOLLOW-UP: Immobilization and cold therapy were started as the first line of treatment, then stretching and gradual loading were added. The patient was able to play after 3 weeks. DISCUSSION: AbdH strain is a rare cause of heel pain, but it should be kept in mind, especially when a suspected mechanism of injury occurs.

Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020).

Vietnam's goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant Plasmodium falciparum malaria to key antimalarials, particularly dihydroartemisinin-piperaquine (DHA-PPQ). The custom targeted NGS amplicon sequencing assay, AmpliSeq Pf Vietnam v2, targeting drug resistance, population genetic- and other markers, was applied to detect genetic diversity and resistance profiles in samples from 8 provinces in Vietnam (n = 354), in a period of steep decline of incidence (2018-2020). Variants in 14 putative resistance genes, including P. falciparum Kelch 13 (PfK13) and P. falciparum chloroquine resistance transporter (Pfcrt), were analyzed and within-country parasite diversity was evaluated. Other targets included KEL1-lineage markers and diagnostic markers of Pfhrp2/3. A concerning level of DHA-PPQ resistance was detected. The C580Y mutation in PfK13 was found in nearly 80% of recent samples, a significant rise from previous data. Vietnam has experienced a significant challenge with the spread of DHA-PPQ resistant malaria parasites, particularly in the provinces of Binh Phuoc and Gia Lai. Resistance spread to high levels in Binh Thuan prior to the country-wide treatment policy change from DHA-PPQ to pyronadine-artesunate (PA). A complex picture of PPQ-resistance dynamics was observed, with an increase of PPQ-resistance associated Pfcrt mutations, indicating an evolutionary response to antimalarial pressure. Additionally, the compensatory mutation C258W in Pfcrt, which increases chloroquine (CQ) resistance while reversing PPQ resistance, is emerging in Gia Lai following the adoption of PA as the first-line treatment. This study found high levels of multidrug resistance, with over 70% of parasites in 6 out of 8 provinces showing significant sulfadoxine-pyrimethamine (SP) resistance and widespread chloroquine-resistant Pfcrt haplotypes. We also report an absence of P. falciparum histidine rich protein 2 and 3 (Pfhrp2/3) gene deletions, ensuring the continued reliability of HRP2/3-based rapid diagnostic tests. P. falciparum populations in Vietnam are becoming more isolated, with clonal populations showing high geographical clustering by province. The central highlands, particularly Gia Lai province, have the highest residual malaria burden but exhibit low diversity and clonal populations, likely due to the pressures from the antimalarial drugs and targeted national malaria control program (NMCP) efforts. In conclusion, examining a broad panel of full-length resistance genes and SNPs provided high-resolution insights into genetic diversity and resistance evolution in Vietnam, offering valuable information to inform local treatment and intervention strategies.

Cranial vault expansion in treatment of paediatric idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a rare clinical entity in the paediatric population. Clinical presentation is mostly similar to adult counterpart and can include headaches, vomiting, papilloedema, deterioration in visual acuity or fields, and 6th cranial nerve palsy, leading to significant morbidity. Therapeutic lumbar puncture and medical treatment with acetazolamide are usually the first-line treatments. In a minority of refractory cases, particularly where visual function is threatened, CSF diversion has been traditionally used in clinical practice. CSF diversion in IIH patients can be associated with high rate of shunt malfunction and revision due to small ventricular size leading to repeated procedures. We describe our experience with cranial vault expansion as a method of treatment of paediatric IIH cases refractory to medical treatment as a CSF diversion sparing method. Following review of IIH cases undergoing surgical treatment in our unit over 15years (years 2009-2024), cases receiving cranial vault expansion as primary surgical treatment were selected and further analysed. Inclusion criteria were paediatric cases (age < 16) undergoing vault expansion as first surgical treatment for IIH refractory to pharmacological treatment for vision-threatening papilloedema. All cases were discussed within multidisciplinary meeting and selected following consideration of all management options. Over the studied period, we identified two cases of refractory IIH with severe papilloedema undergoing cranial vault expansion as primary shunt-sparing surgery. Both patients presented with symptoms of headaches, vomiting, and blurred vision with ophthalmological confirmation of severe papilloedema despite pharmacological therapy. Following multidisciplinary discussions, both underwent successful supratentorial vault expansion. Pharmacological treatment was discontinued in both cases following surgery. Evaluation at latest follow-up showed resolution of symptoms and papilloedema with no need for subsequent cerebrospinal fluid diversion at the latest follow-up. Cranial vault expansion is a viable and safe alternative surgical option in paediatric IIH cases refractory to medical treatment obviating the need for repeated shunt procedures. In cases with extremely small ventricles or where parental choice precludes CSF diversion, cranial vault expansion can be considered.

Comparison of antifungal drugs in the treatment of invasive pulmonary aspergillosis: a systematic review and network meta-analysis.

Voriconazole, isavuconazole, and amphotericin (AmB) formulations are currently recommended to treat invasive pulmonary aspergillosis (IPA). We aimed to estimate the efficacy of different antifungal drugs in the initial treatment of IPA. We included all available randomized controlled trials (RCTs) evaluating first-line treatments for IPA by searching PubMed, Medline, EMBASE, the Cochrane Library, and the ClinicalTrials.gov database. We performed a network meta-analysis to compare the relative efficacy of different drugs in treating IPA. The primary outcomes were the overall response and all-cause mortality (ACM). Eight studies were identified that compared different drugs including voriconazole, isavuconazole, posaconazole, anidulafungin, liposomal AmB (L-AmB) at standard, high and low doses (3-5 mg/kg/d; 10 mg/kg/d; 1 mg/kg/d), AmB deoxycholate (dAmB) and amphotericin B colloidal dispersion (ABCD). We found that second-generation triazole antifungal drugs containing voriconazole, isavuconazole, and posaconazole exhibited significantly superior overall response to dAmB and ABCD. Voriconazole was ranked as the best drug on network rank analysis. We found no difference in efficacy between triazole antifungals and L-AmB. A combination of voriconazole with anidulafungin, isavuconazole and voriconazole showed significantly better safety than dAmB. The efficacy of second-generation triazole antifungal drugs for the first-line treatment of IPA is comparable with L-AmB and is better than both dAmB and ABCD. Isavuconazole may show better safety than voriconazole and posaconazole. Combination therapy with voriconazole and anidulafungin may serve as an alternative option for IPA patients with limited drug tolerance. https://inplasy.com/.

Syndrome of Inappropriate Antidiuresis.

Syndrome of inappropriate antidiuresis (SIAD)-the most frequent cause of hypotonic hyponatremia-is mediated by nonosmotic release of arginine vasopressin, which promotes water retention by activating renal vasopressin type 2 (V2) receptors. There are numerous causes of SIAD, including malignancy, pulmonary and central nervous system diseases, and medications. Rare activating mutations of the V2 receptor can also cause SIAD. Determination of the etiology of SIAD is important because removal of the stimulus for inappropriate arginine vasopressin secretion offers the most effective therapy. Treatment of SIAD is guided by symptoms and their severity, as well as the level of plasma sodium. In the absence of severe symptoms, which require urgent intervention, many clinicians focus on fluid restriction as a first-line treatment. Second-line therapeutic options include loop diuretics and salt tablets, urea, and V2 receptor antagonists.

The effect of transition timing of regorafenib on treatment outcomes in unresectable hepatocellular carcinoma: a real-world study.

Regorafenib is the recommended second-line therapy for unresectable hepatocellular carcinoma (uHCC). Our study aimed to assess the effect of transition timing to second-line therapy with regorafenib on treatment outcomes in uHCC patients. In this retrospective study, patients were categorized into prompt transition group (PT group) or delayed transition group (DT group) based on the transition timing to second-line therapy with regorafenib following the first or subsequent occurrence of progressive disease during first-line treatment. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. There were 85 and 122 patients in the PT and DT groups, respectively. The PT group demonstrated significantly better median PFS [4.5months (95% CI 3.8-6.0) vs. 3.4months (95% CI 2.8-4.1); HR 0.641; 95% CI 0.478-0.859; p = 0.003], ORR (24.7% vs. 9.8%, p = 0.007), DCR (69.4% vs. 54.9%, p = 0.049), and median OS [17.5months (95% CI 13.4-not reached) vs. 10.4months (95% CI 7.9-15.6); HR 0.613; 92% CI 0.432-0.871, p = 0.006] compared to the DT group. Moreover, the overall safety profiles were comparable between groups. The prompt transition to second-line therapy with regorafenib following first-line treatment progression suggests better treatment outcomes and potentially longer survival than in patients who delay the transition to second-line therapy.

β-Lactam Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus Infective Endocarditis

Infective endocarditis (IE) caused by Staphylococcus aureus is associated with high mortality, approximately 20% to 30%, mostly in the first month, with no improvement in recent decades. Current opinion is that antistaphylococcal penicillin and cefazolin are equally effective in treating methicillin-susceptible S aureus (MSSA) IE, and both are recommended as possible first-line treatments. Most MSSA strains carry the β-lactamase blaZ gene, and some blaZ-positive strains exhibit an inoculum effect, meaning increased minimum inhibitory concentrations at high inoculum. This reduced susceptibility to an antibiotic at high bacterial inoculum may be particularly relevant in IE, where vegetations have very high bacterial densities. To evaluate the association between phenotypic characteristics of S aureus isolates, β-lactam used, and outcome in patients with MSSA IE. This retrospective case series included MSSA cases treated at 3 French university hospitals between February 2016 and February 2022. The study included patients who had clinical isolates available and had definite or possible S aureus IE that involved native or prosthetic valves. Data were analyzed from July 2023 to June 2024. MSSA isolates were tested for the presence of blaZ and for inoculum effects to cefazolin and oxacillin. The association between first-month mortality and the β-lactam used, the presence of blaZ, and the presence of an inoculum effect to the treatment received was evaluated. This study included 216 patients with MSSA IE (median [IQR] age, 65 [49-73] years; 152 [70.4%] male) who were treated with antistaphylococcal penicillin (139 [64.4%]) or cefazolin (77 [35.6%]). One-month mortality of left-sided IE was 44 of 180 patients (24.4%), with no overall difference between patients treated with antistaphylococcal penicillin or cefazolin. However, 1-month mortality was higher in patients infected with blaZ-positive strains than with blaZ-negative strains (38 of 129 [29.5%] vs 6 of 51 [11.8%]; P = .01), and with strains with an inoculum effect to the β-lactam received than with strains without an inoculum effect (25 of 62 [40.3%] vs 13 of 67 [19.4%]; P = .005). On multivariable analysis, the presence of an inoculum effect was independently associated with first-month mortality (HR, 2.84; 95% CI, 1.28-6.30; P = .01). In this case series of MSSA IE, the presence of an inoculum effect to the β-lactam received was a risk factor for death in the first month. Phenotyping MSSA isolates for inoculum effect may guide β-lactam choice and improve outcomes.

Efficacy and safety of oral propranolol and topical timolol in the treatment of infantile hemangioma: a meta-analysis and systematic review.

Propranolol, a nonselective β-blocker, is the first-line treatment for infantile hemangioma (IH). Topical timolol has recently been proposed as a novel IH treatment with fewer adverse effects. This study was conducted to compare the efficacy and safety of oral propranolol and topical timolol for treating IH. Studies were included after searching PubMed, Embase, Web of Science, and the Cochrane Library via the keywords of "propranolol", "timolol", "infantile hemangioma" and their synonyms. A meta-analysis with pooled odds ratios was performed using the fixed-effect model. Seven articles with 2071 patients were included in this meta-analysis. Compared with topical timolol, oral propranolol had a greater response rate (OR = 2.12, P < 0.001), but it was also associated with a greater risk of adverse events (OR = 2.31, P < 0.001). For superficial IH, timolol demonstrated similar efficacy to propranolol (OR = 1.28, P = 0.34) but with fewer adverse events (OR = 2.30, P = 0.001). Additionally, compared with topical timolol, propranolol at a dosage of 2mg/kg/d had a better response rate (OR = 2.62, P < 0.001), whereas the 1.0∼1.5mg/kg/d propranolol group showed no significant difference (OR = 1.34, P = 0.38). Oral propranolol presents superior therapeutic efficacy in the treatment of IH compared to topical timolol. However, topical timolol can serve as an alternative to oral propranolol for treating superficial IH, providing similar efficacy with fewer adverse effects. Additionally, propranolol at a dosage of 2mg/kg/d offers greater efficacy with a comparable safety profile, whereas the 1.0∼1.5mg/kg/d propranolol dosage shows no significant difference in efficacy compared to timolol but is associated with more adverse events. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024603724, identifier CRD42024603724.

Sea Hare Hydrolysate Reduces PD-L1 Levels in Cancer Cells and Mitigates Rheumatoid Arthritis Ina Collagen-Induced Arthritis Mouse Model.

Our previous study highlighted the anticancer potential of sea hare hydrolysate (SHH), particularly its role in regulating macrophage polarization and inducing pyroptotic death in lung cancer cells through the inhibition of signal transducer and activator of transcription 3 (STAT3). These findings prompted us to investigate additional features of immune-oncology (I-O) agents or adjuvants, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition and their association with rheumatoid arthritis (RA) risk, to explore the potential of SHH as an I-O agent or adjuvant. In this study, we investigated the effects of SHH on PD-L1 levels in various cancer cell types and assessed its effectiveness in treating RA, a common side effect of I-O agents. Our results showed a marked reduction in PD-L1 levels in multiple cancer cell lines and decreased PD-1 and PD-L1 levels in tumor-associated macrophages. In a mouse model with collagen-induced arthritis (CIA), SHH exhibited anti-inflammatory effects comparable to methotrexate (MTX), a first-line treatment for RA. Both the SHH and MTX groups had significantly lower arthritis scores and paw thickness compared to the CIA group. Additionally, SHH or MTX treatment effectively reduced elevated levels of anticollagen type II (CII) antibodies and proinflammatory cytokines (IL-1β, IL-6, and TNF-α). Histopathological analysis revealed that SHH and MTX treatments notably mitigated arthritic inflammation, synovial hyperplasia, and loss of articular cartilage and bone. Micro-CT scans showed reduced articular destruction in the SHH and MTX groups. These findings indicate that SHH treatment decreases PD-L1 levels in cancer cells and reduces the severity of CIA by exerting anti-inflammatory effects. Therefore, SHH holds promise as an I-O agent without side effects such as exacerbation of RA.