Prior Treatment Research Articles

Updated efficacy of anti-TROP2 ADC ESG401 for first-line metastatic TNBC in phase 1b study.

2 Background: ESG401, a novel ADC comprising a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to SN-38, with a Drug-Antibody Ratio of 8 and a stable cleavable linker, demonstrated preliminary efficacy and tolerability in the Phase Ia trial (Ma, ASCO 2023). This report presents updated results from the first-line mTNBC cohort of the Phase Ib trial and results from patients with brain metastases. Methods: Patients (pts) aged ≥18 years with confirmed local advanced/unresectable or metastatic TNBC, without prior metastatic treatment, received ESG401 (16 mg/kg IV on Day 1,8, and 15, with a 28-day cycle) until unacceptable toxicity, progressive disease, or consent withdrawal. Results: As of the cutoff date (Apr 7th, 2024), 24 pts in the cohort received ≥1 dose of ESG401. Median age was 53 years (range: 33-73), 33.3% were ECOG 0, 25.0% were de novo stage IV, 70.8% had visceral disease (8.3% brain, 33.3% liver, 50.0% lung). Updated efficacy results are shown in the Table. Thirteen pts (68.4% of 19 efficacy evaluable pts) remained on treatment, with the longest on-treatment duration being 10.3 mons. Median PFS has not been reached. Two pts in this cohort had brain metastases, with one achieving a complete intracranial response and an overall response of PR, and the other demonstrating overall PR with a -13.8% reduction in brain lesion size. Totally 16 pts with brain metastases were enrolled in the entire Phase Ia/1b trials, for these pts, the best overall intracranial response rate was 31%, with an intracranial disease control rate of 75%, while the corresponding overall response rate and disease control rate were 50% and 69%, respectively. The response of intracranial lesions to the treatment is consistent with that of extracranial lesions. The safety profile of ESG401 remained consistent with previous reports, showing no new or unexpected safety signals. Conclusions: ESG401 monotherapy demonstrates promising antitumor activity in 1L mTNBC pts, characterized by a high response rate and durable response. The ORR numerically exceeded that reported in the BEGONIA Study arm 7 in which pts with the same indication were treated with TROP-2 ADC and PD-L1 combination therapy. Additionally, ESG401 shows clear potential for treating HER2-negative breast cancer with brain metastases, including mTNBC and HR+/HER2- BC. These results support further clinical investigation of ESG401. Clinical trial information: NCT04892342 . [Table: see text]

Differential expression in potential therapeutic target protein by treatment in small cell lung cancer with and without transformation.

202 Background: Small cell lung cancer (SCLC) is a disease with a poor prognosis. Besides combination strategy with immune checkpoint inhibitors (ICIs) and cytotoxic agents, antibody-drug conjugates (ADCs) and bispecific T-cell engagers (BiTE) are being developed. These drugs target tumor-associated surface protein. Whether prior treatment affect the transition of protein expression has not been fully investigated especially in the era of ICIs. The purpose of this study is to evaluate changes in protein expression in SCLC tissues before and after treatment. Methods: We included patients diagnosed with SCLC by surgery or biopsy and underwent re-biopsy after treatment (non-transformed group) at the National Cancer Center Hospital between 2014 and 2023. Patients who were initially diagnosed with non-small cell lung cancer and underwent transformation to SCLC (transformed group) were also included. Tissues were obtained by surgery, bronchoscopy, or CT-guided biopsy with an interval of at least 100 days. We investigated clinicopathological features in paired specimens focusing on DLL3, ASCL1, NEUROD1, POU2F3, and YAP1, which have been reported to be expressed in SCLC, as well as tumor-associated surface proteins potentially related to novel drug development. Results: Fourteen non-transformed group cases and 9 transformed group cases were included. Of these, pathology specimens were evaluable in a total of 15 cases: 9 for the non-transformed group and 6 for the transformed group. The median age was 68 years, 11 (73%) were male, 11 (73%) were smokers, 8 (53%) were in clinical stages I-IIIA, 1 (7%) in stages IIIB and 6 (40%) in stage IV. Among the transformed group, 4 of them were treated by Osimertinib before transformation. Progression free survival from first-line therapy was 298 days (255-446) vs. 314 days (245-NA) and overall survival was 1239 days (567-NA) vs. NA days (517-NA), respectively for non-transformed group and transformed group. For both these group of cases, we have evaluated several protein expressions as described above. The transition of these proteins within each group is presented in the conference. Conclusions: In this study, we focused not only on proteins already reported to be expressed in SCLC, but also on proteins that are potential new therapeutic targets and evaluated changes in protein expression. [Table: see text]

Efficacy of combination of immune checkpoint inhibitors, chemotherapy, and targeted therapy in advanced/refractory cancer.

41 Background: The treatment of advanced/refractory malignancies continues to pose a major challenge, and it is associated with poor outcome. It has been shown that in some cancers, the combination of chemotherapy (CT) with immune checkpoint inhibitors (ICIs), or CT with targeted therapy (TT), are superior to chemotherapy alone. Consequently, in our treatment program (ICTriplex), TT was added to CT plus ICIs. These three modalities have convergent efficacy with divergent toxicity. Our prior data were previously reported (1-3). Methods: Treatment with ICTriplex was highly personalized and was tailored to the individual patient and their specific cancer. It was designed based on diagnosis, prior therapy, and genomic profiling. Between March 2017 and January 2024, 56 patients (pts) with advanced malignancies were treated: 31 females and 25 males, with a median age of 58. Tumor types included: lung (12), pancreas (8), colorectal (8), biliary tract (5), breast (4), stomach (4), melanoma (3), ovary (3), sarcoma (3), cervix (2), glioblastoma (2), Hodgkin’s (1), and thymoma (1). 43 pts received prior therapy: 14 received ICIs, 23 TT, and 42 CT. The agents used in ICTriplex were: 6 ICIs primarily nivolumab and pembrolizumab, 12 CT primarily taxanes, gemcitabine, and platinum, and 23 TT, primarily bevacizumab and erlotinib. Response was evaluated by both PET/CT and CT scans. A complete remission was achieved when metabolic activity completely resolved on PET/CT. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator. Results: The overall response rate (ORR) was 88%. A complete remission (CR) occurred in 29 pts (52%), and a partial remission (PR) in 20 pts (36%). Of the 12 pts with lung cancer, 9 (75%) achieved CR and of these, 4 pts had brain metastases that completely resolved without radiation. Of the 8 pts with pancreatic cancer, 4 (50%) achieved CR. 4 of 5 pts with biliary tract cancer achieved CR. Toxicity was reasonable in all pts except for 3 who died from complications possibly related to ICIs. The median PFS was 11 months, and the median OS was 15 months. The achievement of CR and the PD-L1 + status, resulted in a statistically significant better PFS (p= 0.00; p= 0.02) and OS (p=0.00; p= 0.005). Patients with lung cancer showed a better PFS (p= 0.02) with the median at 19 months, and the median OS was 36 months. Potential predictors of unfavorable prognosis, such as receiving prior treatment, did not impact patients' clinical outcome. Conclusions: ICTriplex is a very effective treatment for advanced cancer that has become resistant to conventional therapy or with no available standard therapy. We strongly recommend this therapeutic approach for the treatment of such patients. 1. ASCO 2019 (e14254) 2. ASCO 2020 (e15150) 3. ASCO 2022 (e14590).

Efficacy and Safety of KRASG12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study

IntroductionKRAS glycine-to-cysteine substitution at codon 12 (G12C) mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study. MethodsEligible patients with NSCLC with KRAS G12C who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. The primary endpoint was confirmed objective response rate assessed by an independent radiological review committee (IRRC) as per Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints were safety, IRRC-confirmed disease control rate, duration of response, progression-free survival (PFS), and overall survival. ResultsAs of December 13, 2023, 116 patients were enrolled (Eastern Cooperative Oncology Group Performance Status 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1 or anti-PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per the IRRC assessment, the confirmed objective response rate was 49.1% (95% confidence interval [CI]: 39.7–58.6), and the disease control rate was 90.5% (95% CI: 83.7–95.2). The median duration of response was not reached whereas disease progression or death events occurred in 22 patients (38.6%), and the median PFS was 9.7 months (95% CI: 5.6–11.0). overall survival data was immature. Treatment-related adverse events (TRAEs) occurred in 107 patients (92.2%) whereas 48 patients (41.4%) had equal to or higher than grade three TRAEs. Common TRAEs were anemia (44.8%), increased alanine aminotransferase (28.4%), increased aspartate aminotransferase (27.6%), asthenia (26.7%) and presence of protein in urine (25.0%). TRAEs leading to treatment discontinuation occurred in nine patients (7.8%). In biomarker evaluable patients (n = 95), all patients had positive KRAS G12C in tissue whereas 72 patients were blood-positive and 23 were blood-negative for KRAS G12C. Patients with KRAS G12C in both blood and tissue had higher tumor burden at baseline (p < 0.05) and worse PFS (p < 0.05). Tumor mutation profiling identified tumor protein p53 (45.3%), serine/threonine kinase 11 (STK11) (30.5%), and kelch-like ECH-associated protein 1 (21.1%) as the most common genes co-mutated with KRAS G12C. Among 13 genes with mutation frequency equal to or higher than 5%, mutations of six genes (STK11, kelch-like ECH-associated protein 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, DNA polymerase epsilon, SMAD family member 4, and BMP/retinoic acid-inducible neural-specific protein 3) were significantly associated with worse PFS (p < 0.05). Mutation in STK11 was also found to have a significant association with higher tumor burden at baseline and lower response rate (p < 0.05). ConclusionsIBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new treatment option for KRAS G12C-mutant NSCLC.

Analysis of risk factors affecting postoperative neurological recovery in patients with cervical spine fracture in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease that mainly affects the spine and involves the sacroiliac and peripheral joints. Low-energy trauma can often lead to spinal fractures and spinal cord injuries (SCIs), the treatment of AS is challenging. The prognosis of neurological function in patients with AS cervical fracture and SCI is a major problem that must sought clinician attention on urgent basis. A total of 106 patients with AS cervical fractures who underwent surgical treatment at Shanghai Changzheng Hospital between August 2009 and 2021 were included in this study. All the patients were divided into 2 groups (improved group and the control group) based on their neurological function improvement at 1 year mark after the surgery. The baseline characteristics, perioperative factors, and procedural outcomes of all the patients including injury type, AS drug treatment, the injured segment, ossified anterior longitudinal ligament injury, spinal hypersignal, decompression time window, operation duration, blood loss, preoperative and postoperative American Spinal Injury Association (ASIA) score were recorded and analyzed. Among the 106 patients, 79 demonstrated improved neurological function at 1 year mark after the surgery. Binary univariate logistic regression analysis revealed significant differences in injury type (P = .018), ossified anterior longitudinal ligament injury (P = .01), operation duration (P = .002), spinal hypersignal (P = .001), preoperative ASIA score (P < .001), and prior AS drug treatment (P = .012). No significant differences were observed in the other variables (P > .05). Binary multivariate logistic regression analysis identified spinal hypersignal (OR = 37.185, P = .028), preoperative ASIA score (OR = 0.16, P = .012) and previous AS drug treatment (OR = 0.296, P = .049) as factors associated with postoperative neurological function improvement. The preoperative ASIA score and previous drug treatment of AS were identified as protective factors affecting the improvement of neurological functions in patients with AS cervical fracture after surgery. Preoperative T2-weighted spinal hypersignal was identified as an independent risk factor affecting the improvement of neurological function recovery in patients with AS cervical fracture after the surgery.

Treatment Patterns and Survival Outcomes Among Androgen Receptor Pathway Inhibitor-Experienced Patients With Metastatic Castration-Resistant Prostate Cancer

BackgroundThere is limited real-world data regarding subsequent treatment utilization and clinical outcomes following initial androgen receptor pathway inhibitor (ARPI) exposure for the treatment of advanced prostate cancer. This study aimed to address this evidence gap. MethodsElectronic health records during 01/01/2013-07/31/2022 from Flatiron Health were used to identify adults with mCRPC, who had prior exposure to ARPIs (irrespective of the setting) and ≥1 post-ARPI line of therapy (LOT) in the mCRPC setting (index therapy: the first eligible LOT in the mCRPC setting). Treatment patterns and survival outcomes following the initiation of index therapy were reported. ResultsAmong 804 ARPI-experienced mCRPC patients, 459 patients (57.1%) received another ARPI as their index therapy and 192 (23.9%) received chemotherapy as their index therapy. In the overall population, median time on the index therapy and median time from index therapy to next therapy were 4.1 and 6.2 months, respectively. Median overall survival and radiographic progression-free survival from the initiation of index therapy were 15.1 and 7.0 months, respectively. ConclusionsIn this real-world analysis, more than half of patients attempted at least 1 additional ARPI in the mCRPC setting, despite prior treatment with ARPIs. The short treatment duration and survival time highlight the unmet need for additional, effective therapies that may improve clinical outcomes in this population.

Levonorgestrel intrauterine system versus dienogest effect on quality of life of women with deep endometriosis: a randomized open-label clinical trial

ABSTRACT Women with deep infiltrating endometriosis (DIE) can benefit from the use of progestins. Our aim is to explore if levonorgestrel-releasing intrauterine system (LNG-IUS) non inferior to dienogest (DNG) in improving deep endometriosis women’s quality of life (QoL). This randomized open-label clinical trial included forty women with DIE assessed using clinical history and physical examination, transvaginal ultrasonography and magnetic resonance of the pelvis without any previous surgical treatment, with two treatments arms. The two groups underwent a 3-month washout of hormonal treatments, and then received either DNG or LNG-IUS for 6 months. QoL was assessed prior to and 6 months after the intervention, using the SF36 and the EHP30. DNG and LNG-IUS showed an increase on all domains of the SF36 (p < .001). There was no difference between treatments on the improvement observed (p > .05 for all domains). DNG and LNG-IUS, also, showed improvement on all domains of EHP30 (p < .001), except “relationship with children” and “feelings about pregnancy.” However, there was no statistical difference between treatments for all sections scores (p > .05). The treatment of deep endometriosis symptoms using either DNG or LNG-IUS in women with no prior surgical treatment is associated with improvement in QoL. Trial Registration Number: This trial is registered on “The Brazilian Registry of Clinical Trials (ReBECID: RBR-8fjx2jp),” that is part of Primary Registries in the WHO Registry Network, under the title: “Dienogest versus Levonorgestrel IUS on deep endometriosis patient´s QoL without surgery” on June 14, 2021; https://ensaiosclinicos.gov.br/rg/RBR-8fjx2jp.

Cerebral arterial air embolism after esophageal stenting for recurrence of gastroesophageal junction cancer: a case report.

Cerebral arterial air embolism (CAE) is a rare complication after esophageal stenting, but it can be life-threatening. It is especially a concern for those with a history of previous gastrointestinal cancer therapies. We report a case of CAE after esophageal stenting in a patient with recurrent gastroesophageal junction cancer and a history of multiple cancer treatments. A 71year-old man with a history of a proximal gastrectomy, resection of the lower esophagus, chemotherapy, and radiation presented to our hospital 2weeks after stenting with epigastric and back pain. Mediastinitis was suspected and conservative treatment was begun. The patient suddenly developed altered mental status, left hemiplegia, and anisocoria after drinking water. A brain computed tomography (CT) revealed right-sided predominance of multifocal CAE. Chest and abdominal CT showed a hematoma in the gastric and duodenal wall and an intraluminal hematoma from the esophagus, around the stent, to the upper ileum. CAE was thought to be due to rupture of the recurrent tumor. Unfortunately, despite intensive care, the patient died about 5h after the onset of neurological symptoms. It has been reported that prior treatments, such as chemotherapy and radiotherapy, increase the risk of life-threatening adverse events, including CAE after esophageal stenting. Clinicians should keep in mind the possibility of CAE after esophageal stenting in patients with a history of multiple cancer treatments.

Correlation of Imaging and Hemodynamic Findings with Clinical Outcomes for Diagnosis of Left Renal Vein Compression Syndrome.

Left renal vein compression syndrome (LRVCS) remains a challenging diagnosis. This study aimed to correlate imaging and hemodynamic findings with clinical outcomes for patients with LRVCS. A retrospective review of 66 renal venography procedures with or without intravascular ultrasound (IVUS) was performed from 2017 to 2023 at a single institution. Patients with prior LRVCS treatment or other indications were excluded (n = 11). Primary outcome measure was correlation of catheter-based endovascular (CBE) findings with clinical outcomes (n = 55). Secondary outcome measures included correlation of CBE findings and LRV (i.e., beak) angle > 32°, beak sign, aortomesenteric angle (AMA < 41°), and hilar-to-aortomesenteric ratio (HTAMR ≥ 4.9) on cross sectional imaging. Descriptive statistics, chi-square testing, and ROC analyses were used. Of the 55 patients, 52 (94.5%) were females (median age 31, range 14-72) and 56.4% (n = 31) had a diagnosis of LRVCS on CBE evaluation. A renocaval pressure gradient of ≥ 3mmHg, presence of collaterals, and > 50% area stenosis on IVUS were significantly associated with CBE diagnosis of LRVCS (p < 0.001). Surgical treatment (renal autotransplantation or LRV transposition) was recommended to all patients with CBE diagnosis of LRVCS (n = 31). 81.2% (18/22) of patients who underwent surgery reported symptom resolution or improvement. When the cross sectional imaging measurements were compared with CBE evaluation, AMA was the most sensitive (100%), HTAMR and beak sign were highly specific (93.3%), and beak angle was the most predictive (77.4% sensitivity; 86.7% specificity). CBE diagnosis of LRVCS was highly predictive of surgical candidacy and post-surgical symptom resolution. The presence of collaterals, > 50% area stenosis on IVUS, or a renocaval pressure gradient ≥ 3mmHg had a significant association with a CBE diagnosis of LRVCS.

Case Report: The Sausage Technique using Anorganic Bovine Bone Mineral for Horizontal Bone Augmentation at the Crestal Part of a Posterior Mandibular Ridge: A Case Report.

Following tooth extraction, the alveolar bone goes through a natural remodeling process resulting in a significant bone resorption which may complicate dental implant placement without prior bone augmentation treatment. The sausage technique is a modified guided bone regeneration (GBR) method that has been successfully used for horizontal bone augmentation. This technique was developed to increase the bone growth at the alveolar crest. Although the sausage technique uses a combination of autograft chips and xenograft particles with a native collagen membrane, several studies have questioned whether adding autograft chips is essential for bone formation with guided bone regeneration. Moreover, harvesting the bone graft may increase the donor site morbidity and patient discomfort. This case report aimed to investigate the bone gain radiologically when the sausage technique was applied to treat a healthy, thirty-year-old patient with a horizontal defect in the posterior mandibular region using anorganic bovine bone mineral (ABBM) particles with Jason membrane, assess the implant primary stability in the augmented ridge, and present the surgical procedure steps in details. After nine months of healing, the cone-beam computed tomography (CBCT) revealed approximately 4.32 mm of bone gain at the alveolar crest in the buccal-lingual direction. The graft particles were well integrated into the newly formed bone. Two implants were inserted with an insertion torque of 35 N/cm. The ISQ values were 76 for the most anterior implant and 78 for the posterior implant. Within the limitations of this case report, the sausage technique using ABBM particles without autograft chips was an effective approach in achieving the prerequisite bone width at the crest in cases with horizontal bone defects.

Selinexor in combination with dexamethasone with or without bortezomib in heavily pretreated multiple myeloma: A case series

AbstractThis report describes the characteristics and outcomes of 18 heavily pretreated patients with multiple myeloma (MM) who were subsequently treated with selinexor. This is a case series of 18 patients with MM who were treated with selinexor and dexamethasone (Sd) or selinexor, bortezomib, and dexamethasone (SVd) in 12 hospitals in the UK between 2019 and 2021. Eight patients received Sd and 10 patients received SVd. Patients received a median of five prior treatment lines, including immunomodulatory agents in 94% and proteasome inhibitors in 94%. Ten patients (55%) had triple‐class refractory disease. Six of the 12 evaluable patients achieved ≥partial response. The median progression‐free survival was 5.6 months, which was higher with SVd (5.7 months) than with Sd (2.1 months). The results support a treatment benefit of selinexor in heavily pretreated patients and support the notion that selinexor may overcome resistance to prior therapies, with no new safety concerns arising.

Comparing Level of Happiness and Depression Between Turkish and International Medical Students

This cross-sectional study was aimed to compare happiness and depression levels among group Turkish and international medical students in Istanbul, Turkey. Data were collected through an online survey that included demographic inquiries, the Oxford Happiness Scale, and Beck’s Depression Inventory II. Significant contrasts emerged in demographic and lifestyle factors between Turkish and international students. Turkish medical students displayed a higher prevalence of unhappiness, although this difference was not statistically significant (66.3% for Turkish students vs. 59.1% for international students; χ² = 2.472, p = 0.116). Conversely, no marked differences were observed in the severity of depression between the two groups (χ² = 0.028, p = 0.986). Conversely, no marked differences were observed in the severity of depression between the two groups (χ2 = 0.028, p = 0.986). Logistic regression analyses revealed noteworthy associations. Factors such as age, academic phase, family history of psychiatric illness, and prior psychiatry treatment were linked to heightened odds of experiencing unhappiness among students. Similarly, significant predictors of depression included a family history of depression and prior psychiatry treatment. However; gender, age, relationship status, accommodation, alcohol consumption, smoking habits, and repeated academic years did not exhibit significant associations with unhappiness among the sampled medical students. While the models demonstrated modest explanatory power, these findings emphasize the urgent need to address mental health issues among medical students. Tailored interventions targeting specific vulnerable subgroups are crucial and further research is needed to identify additional factors contributing to psychological distress in this demographic.

Forensic application of sandpaper spray ionization mass spectrometry (SPS-MS): Direct analysis of solid pharmaceutical formulations and edible cannabis products.

In this work, we employed a new ambient ionization mass spectrometry technique, sandpaper spray mass spectrometry (SPS-MS), as an efficient tool to analyze pills and tablets of pharmaceutical formulations. The following samples were analyzed: regulators of blood pressure, cholesterol, and diabetes, and drugs for the treatment of erectile dysfunction (ED). Additionally, a hard candy of Cannabis sativa containing Δ9-tetrahydrocannabinol (Δ9-THC) and its related isomer cannabidiol (CBD) was also evaluated. The surfaces of the samples, without any prior treatment, were sanded onto triangular-cut sandpaper, and full MS scans (and MS/MS) were acquired in both positive and negative ionization modes. SPS-MS (and MS/MS) allowed for prompt detection of the active pharmaceutical ingredients (APIs) in each formulation. Other components of the formulations, added as excipients, were also tentatively identified. The results described herein indicate that the SPS-MS technique can be applied to fast screening of pills and tablets being potentially used as an efficient tool to detect counterfeit pharmaceutical and illicit products, a current issue of increasing concern.

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL

AbstractThe effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL), particularly the influence of previous InO response and the timing of administration. We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. When InO-exposed patients were stratified according to prior InO response, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

Combination Therapy of Lenvatinib and Hepatic Arterial Infusion Chemotherapy Using Cisplatin With Lipiodol and 5-Fluorouracil: A Potential Breakthrough Therapy for Unresectable Advanced Hepatocellular Carcinoma.

In 2021, the LEOPARD trial reported that the combination of lenvatinib+one-shot cisplatin infusion might contribute to improving the results of conventional advanced hepatocellular carcinoma (HCC) treatment. Thus, combination therapy with lenvatinib and catheterization has emerged as a focal point in treating advanced HCC. Conversely, the New FP regimen consists of low-dose cisplatin (CDDP) combined with 5-fluorouracil (5-FU) and lipiodol via hepatic arterial infusion chemotherapy (HAIC), with a high response rate of approximately 70%. Therefore, lenvatinib+New FP (LEN-New FP) may be a more promising treatment for HCC. Here, we report six patients who were administered LEN+New FP and achieved high therapeutic efficacy. Among them, one case had an interesting clinical course, which has been described in detail. This study included six patients who were administered 12 mg or 8 mg of lenvatinib once daily based on a body weight of ≥60 kg or <60 kg, respectively, along with 50 mg of cisplatin in 5-10 mL lipiodol, and a continuous infusion of 5-FU (1500 mg/5 days) infused every 2-4 weeks. Tumor evaluations were performed 4-8 weeks after the initiation of New FP administration and every 8-12 weeks thereafter. The median patient age was 65 years. All patients had a history of prior treatment with atezolizumab and bevacizumab and one of the factors associated with poor overall survival for New FP monotherapy, such as a maximum tumor diameter ≥7 cm and bilobular multifocal distribution. Four (67%) patients had severe vascular invasion. The best objective response and disease control rates were 83% and 100%, respectively. The best response of the target lesion was complete remission in four out of six patients. The LEN-New FP combination for advanced HCC showed a high response rate and was more effective in high-risk patients with factors associated with poor overall survival than that reported with conventional New FP monotherapy. Additionally, LEN-New FP exhibited extremely high objective response and disease control rates and was well tolerated, including in cases where it was considered second- or third-line systemic chemotherapy for advanced HCC. Thus, LEN-New FP can serve as a breakthrough therapy for advanced HCC based on appropriate case selection.

Fungal keratitis among inpatients with corneal ulcers in Thai Binh, Vietnam: A retrospective observational study

Background: Infectious keratitis can be caused by bacteria, fungi, and viruses. Fungi are a common pathogen, especially in developing countries like India, Nepal, and Bangladesh where the prevalence ranges from 20% to 60%. In Vietnam, fungal keratitis accounted for the highest number of keratitis cases in a study conducted at the central eye hospital over a 5-year period (57%). Therefore, it is necessary to collect specific background information connected to the types of fungal keratitis in corneal ulcer cases in this region. Aims and Objectives: The aim of this study was to investigate the prevalence of fungal keratitis and the epidemiological features in 216 cases of fungal keratitis out of a total of 240 cases of infectious keratitis. Materials and Methods: This retrospective study collected secondary data from medical records of 240 inpatients with infectious keratitis who were treated at the ophthalmology hospital in Thai Binh, Vietnam, from January 01st, 2021 to June 30th, 2022. Patients with a positive fungal-directed smear were analyzed in detail for the type of fungus isolated, sociodemographic data, predisposing risk factors, prior treatment modalities, and laboratory results for the distribution pattern of fungus species. Results: Among the 240 cases, 126 (52.5%) were diagnosed with fungal keratitis by direct microscopic examination. Culture results showed the highest rate of Fusarium spp. (43.3%). The age group of 41–60 years was most commonly involved (40.5%). Males were more affected by fungal keratitis than females, (53.2% compared to 46.8%), with farmers being the most common occupation correlated with fungal keratitis (55.6%). The rate of fungal keratitis patients due to agricultural injuries was the highest compared to other risks (47.6%) and most patients self-medicated before going to the hospital, with many not knowing or remembering what medications they had taken (52.4%). Conclusion: The study revealed a high rate of fungal keratitis among the total of infectious keratitis cases in Thai Binh, Vietnam. Fusarium spp. was the most commonly isolated fungi. The study also highlighted the impact of agricultural injuries on fungal keratitis, especially in regions like Thai Binh.

Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study.

Isavuconazole is a relatively new antifungal agent indicated for the management of various invasive fungal diseases (IFDs), including invasive aspergillosis. Information on real-world experience with isavuconazole is scarce. This retrospective observational study aimed to describe the usage of isavuconazole in clinical practice with an in-depth evaluation of individual isavuconazole exposure. Patients treated with isavuconazole were evaluated based on retrospective data, including therapeutic drug monitoring (TDM) data and efficacy and safety data. Additionally, we calculated the individual isavuconazole exposure described by the average AUC24 over the first 7 days of treatment by means of non-linear mixed-effects modelling and compared this with the currently desired lower target AUC of 60 mg·h/L. Ninety-nine patients treated with isavuconazole were evaluated. In our real-life cohort, isavuconazole was often deployed off-label in patients with non-classical host factors and infections with non-Aspergillus and non-Mucorales species. Isavuconazole was most often chosen for its safety profile, even after prior triazole treatment with manifestations of toxicity. TDM and subsequent dosage adjustments were frequently performed. The individual average AUC24 over 7 days was above 60 mg·h/L in 29 out of 77 (37.7%) patients. This overview provides practical insights that can aid clinicians in the management of their patients with IFD. Our study shows that isavuconazole was used in a diverse patient population and was well tolerated overall. Individual isavuconazole exposure reflected by the average AUC24 over the first 7 days of treatment was generally low and variable. Dosage adjustments following TDM were frequently performed. Our experience shows that isavuconazole is a feasible alternative after prior azole treatment.

Outcomes of Acute Promyelocytic Leukaemia in Paediatric Patients: Insights from a Low-Middle-Income Country.

To describe the prognostic variables and course of paediatric acute promyelocytic leukaemia (APL) in Pakistan. Cohort study. Place and Duration of the Study: Department of Paediatric Oncology, Combined Military Hospital, Rawalpindi, Pakistan, from January 2012 to December 2022. Patients aged 1-15 years, clinically confirmed APL with promyelocytic leukaemia- retinoic acid receptor alpha (PML-RARA) were enrolled. Initial admission included a thorough examination, recording demographic and clinical data, reporting time, prior treatment, and socioeconomic status. Statistical analysis used SPSS 25.0, with significance at p <0.05. This study included 50 cases of APL. Out of which, 32 (64%) were males and 18 (34%) were females. The mean age at diagnosis was 7.02 ± 3.86 years. Pallor (96%) and fever (88%) were common presentations. The average white blood cell count was 28.70 ± 35.39 x109/L. Treatment protocols include 48% International Consortium for Childhood (ICC)-APL, and 52% arsenic trioxide (ATO). High-risk cases were 54%. Neutropenic fever and differentiation syndrome were common induction complications. Delays over one month increased induction deaths (6.7 to 35%, p = 0.011), reducing disease-free survival (DFS), (76.7 to 35%, p = 0.001), and overall survival (OS), (80 to 45%, p = 0.007). After 40.90 ± 45.19 months' follow-up, 10-year OS and DFS were 66.0% and 60.0%, respectively. The best OS and DFS, at 80%, were observed in standard-risk cases treated with ATO. Neutropenic fever and bleeding were the primary causes of mortality in paediatric APL induction. Treatment delay was a key prognostic factor. ATO-based therapy offered safer, improved DFS, and OS suitable for primary healthcare settings. Acute promyelocytic leukaemia, Chemotherapy, Neutropenic fever.

Predictors of the efficacy of vedolizumab in patients with ulcerative colitis.

Vedolizumab is a treatment option for ulcerative colitis but data on predictors of treatment response remain insufficient to establish personalized treatment strategies. We aimed to investigate the real-world effectiveness of vedolizumab in adult patients with ulcerative colitis and explore factors involved in predicting treatment response. This single-center, single-arm, prospective observational study included 26 patients with clinically active ulcerative colitis patients' characteristics at baseline, epidemiological information, existing treatment, clinical activity index score, endoscopic score, and blood test data were collected. Serum levels of tumor necrosis factors alpha, interferon gamma, interleukin-4, interleukin-6, interleukin-10, interleukin-17, soluble mucosal addressin cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 were measured. Patient characteristics in the remission and non-remission groups were compared based on these parameters. Clinical remission at 6 weeks of treatment occurred in 9 (35%) of the 26 patients. At 14 weeks, clinical remission was observed in 11 patients (42%). There were no significant differences pertaining to age, sex, duration of disease, extent of disease, steroid resistance, or prior treatment with biological agents among the two groups after 14 weeks of treatment. Hemoglobin ≥ 11.5 g/dL (odds ratio, 15.0; 95% confidence interval, 1.50-149; P=0.014) and soluble mucosal addressin cell adhesion molecule 1 ≥ 765 pg/mL (odds ratio, 17.3; 95% confidence interval, 2.36-127; P=0.004) were significant factors. In conclusion, hemoglobin and serum soluble mucosal addressin cell adhesion molecule 1 levels are factors correlated with the therapeutic efficacy of vedolizumab.

Effect of Tongue Position on Facial Morphology of Pakistani Adults and Different Growth Patterns.

To determine the effect of tongue position on facial morphology of Pakistani adults and different growth patterns. Cross-sectional study. Place and Duration of the Study:Department of Orthodontics, Karachi Medical and Dental College, Karachi, Pakistan, from January to April 2021. The study included individuals aged 17 to 30 years with no history of prior orthodontic treatment, absence of wound, burn, or scar tissue in the neck region, comfortable breathing through the nose, absence of deglutition disorder, and a skeletal Class I or II relationship. The exclusion criteria were a cleft lip or palate, or a history of chronic mouth breathing, snoring, or tonsillectomy. According to their skeletal relationships, the subjects were split into three groups; Group I (low-angle), Group II (normal growth), and Group III (high-angle). Vertical growth pattern was assessed on radiograph by interpreting the values of NS / ML (nasion-sella / mandibular plane) angle, and angle formed between FH / ML (Frankfort horizontal plane / mandibular plane). A predesigned proforma was used to record all the measurements made on pre-treatment lateral cephalograms by the sole investigator. Data were analysed using SPSS 24.0. Data from the lateral cephalogram of 79 patients, consisting of 18 (22.8%) males and 61 (77.2%) femaleswho met the inclusion criteria, were analysed.The sample included 15 low-angle, 45 normal vertical growth, and 19 high-angle cases. Fifty participants had Class I skeletal relationships, while 29 had Class II relationships. According to the ANOVA test, FH / ML and NS / ML measurements showed no statistically significant variations in tongue position and growth trends. There was no statistically significant difference between tongue position and facial morphology of Class I or II subjects with different vertical growth patterns. However, there was a statistically sufficient evidence showing the tongue height was greater in Class I skeletal relationship patients as compared to Class II skeletal cases (p = 0.008). Tongue position, Tongue space, Tongue length, Growth pattern.