A real-world retrospective-prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience.

INTRODUCTION: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1. OBJECTIVES AND METHODS: We conducted a retrospective-prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. RESULTS: At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high-risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)-exposed (including both Len-sensitive and Len-refractory pts), and 22% were Len-refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non-hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1-2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow-up of 38 m, median PFS (mPFS) was 16 m and the 1-year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len-naïve (NR), age ≥70 (20 m). In pts exposed to Len, non-refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len-refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). CONCLUSION: IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len-sensitive, independent of age, and cytogenetic risk.

Response to Ceftriaxone in Asymptomatic Neurosyphilis Refractory to Doxycycline and Benzathine Penicillin.

An asymptomatic male in his mid-30s presented with a positive Venereal Disease Research Laboratory (VDRL) test report. He was investigated and detected to be reactive for human immunodeficiency virus (HIV)-1 antibodies. A lumbar puncture revealed cerebrospinal fluid (CSF) VDRL to be reactive at a titer of 1:160 which led to a diagnosis of asymptomatic neurosyphilis. The unavailability of first-line antibiotics necessitated the search for alternative regimens. The patient was administered oral doxycycline 200 mg twice daily for 28 days along with intramuscular benzathine penicillin 2.4 million units once weekly for three weeks. A repeat CSF-VDRL performed six months later with raised titers of 1:320 indicated treatment failure. The patient was then administered ceftriaxone 1 g intramuscularly for 14 consecutive days. A final CSF-VDRL examination performed six months later showed non-reactive titers.

A budget impact model and a cost-utility analysis of reducer device (Neovasc) in patients with refractory angina.

Background: Refractory angina (RA) is a chronic condition characterized by the presence of debilitating angina symptoms due to established reversible ischemia in the presence of obstructive coronary artery disease (CAD). Treatments for this condition have undergone major developments in recent decades; however, the treatment for RA remains a challenge for medicine. In this sense, the Coronary Sinus Reducer System (CSRS) stands as the last line of therapy for ineligible patients for revascularization with reversible ischemia. The purpose of this report is to evaluate the potential burden on the National Health Service (NHS) and measure the health effects in terms of both quantity (life years) and quality-of-life aspects related to the reducer. Methods: Two different economic evaluation models were developed as part of the analysis. The budget impact was developed to estimate the potential burden on the NHS from incremental uptake of the use of the reducer in the target population. The utility cost analysis compares and evaluates the quality of life and health resource use and costs between the two alternatives, based on the research of Gallone et al. A deterministic and probabilistic sensitivity analysis was carried out to characterize the uncertainty around the parameters of the model. Results: In the budget impact analysis (BIA), the reducer is shown to be more expensive in the first 2 years of the model, due to the gradual uptake in the market and the cost of the device. Starting from the third year, assuming maintenance of effectiveness, there are savings in terms of resource absorption in direct healthcare costs arising from hospitalizations, emergency department accesses, coronarography, and visits avoided. Conclusion: The BIA and cost-effectiveness model show that the reducer device, despite an increase in resources absorbed in the first years of implementation and use, has the potential to result in increased quality of life in patients with RA. These costs are largely offset in the short term by the improved clinical outcomes achievable leading to savings from the third year onward in the BIA and a dominance ratio in the cost-utility analysis.

Somatic gene mutation patterns and burden influence outcomes with enasidenib in relapsed/refractory IDH2-mutated AML.

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this large R/R AML patient cohort, targeted next-generation sequencing at baseline (screening) revealed distinct co-mutation patterns and mutational burden between subgroups bearing different IDH2 variants: variant IDH2-R140 was associated with greater mutational burden and was enriched predominantly with poor-risk mutations, including FLT3, RUNX1, and NRAS, while variant IDH2-R172 was associated with lower mutational burden and was preferentially co-mutated with DNMT3A. In multivariable analyses, RAS and RTK pathway mutations were significantly associated with decreased overall survival, after adjusting for treatment arm, IDH2 variant, and mutational burden. Importantly, enasidenib-mediated survival benefit was more pronounced in patients with IDH2-R172 variants.

Risk Factors of the Occurrence and Treatment Failure of Refractory Peritoneal Dialysis-Associated Peritonitis: A Single-Center Retrospective Study From China.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of refractory peritoneal dialysis (PD)-associated peritonitis as well as the risk factors of its occurrence and treatment failure. METHODS: A single-center retrospective cohort study was conducted among 519 patients undergoing PD from January 2007 to October 2021. According to the International Society for Peritoneal Dialysis guidelines, all episodes occurred in our center were divided into two groups: refractory and nonrefractory. Demographic, biochemical, and pathogenic bacteria and treatment outcome data were collected. RESULTS: During the 15-year period, 282 episodes of peritonitis occurred in 166 patients undergoing PD. The refractory rate was 34.0% (96/282). Gram-positive organisms were the leading cause of peritonitis (47.9%); however, gram-negative organisms were predominant in refractory peritonitis (34.4%, p = 0.002). Multiple logistic regression revealed that gram-negative organism-based peritonitis, longer PD duration, and female sex were the significant independent predictors of refractory peritonitis. Among 96 refractory episodes, white blood cell (WBC) count, dialysate WBC on Day 3, and PD duration ≥5 years were the independent risk factors of treatment failure. CONCLUSIONS: Gram-negative organism-based peritonitis, longer PD duration, and female sex were the independent risk factors of refractory peritonitis. Refractory peritonitis with higher WBC count, higher dialysate WBC on Day 3, and PD duration ≥5 years increased treatment failure risk and required immediate PD catheter removal. The timely identification of refractory peritonitis with high risk of treatment failure as well as timely PD catheter removal is important.

Transanal irrigation in children with functional constipation: A systematic review and meta-analysis.

OBJECTIVES: Refractory functional constipation is a challenging condition to manage in children. The use of transanal irrigation (TAI) is well reported in children with neurological disorders as well as anorectal malformations but less so in children with functional disorders of defecation. The objective of our study was to evaluate the effectiveness, safety and outcomes of TAI in children with functional constipation. METHODS: PubMed, Scopus and Google Scholar were searched for publications related to the use of TAI in functional constipation. Data regarding the study design, sample size, patient characteristics, investigator-reported response to TAI and adverse effects were extracted from studies that met the selection criteria. The inverse variance heterogeneity model was used for ascertaining the summary effect in this meta-analysis. RESULTS: The search strategy yielded 279 articles of which five studies were included in the final review. The studies were from the United Kingdom (n = 2), Netherlands (n = 2) and Denmark (n = 1). These studies included 192 children with a median age ranging from 7 to 12.2 years old. The TAI systems used in these studies were: Peristeen (n = 2), Peristeen or Qufora (n = 1), Alterna (n = 1) and Navina (n = 1). The follow-up duration ranged from 5.5 months to 3 years. Eleven (5.7%) children did not tolerate TAI and withdrew from treatment soon after initiation. The pooled investigator-reported success of TAI was 62% (95% CI: 52%-71%). The most common adverse event was pain which was experienced by 21.7% of children. A total of 27 (14%) were successfully weaned off TAI at the last follow-up. CONCLUSIONS: TAI is reported to be successful in 62% of children with refractory functional constipation. There is a need for well-designed prospective trials to evaluate this treatment option in children with refractory functional constipation.

Long-Term Outcome of Photobiomodulation Therapy for Refractory Diabetic Wound After Secretory Carcinoma of the Parotid Gland Surgery: A Case Report.

Objective: To evaluate the efficacy and safety of photobiomodulation therapy (PBMT) in the treatment of diabetic patients with refractory wound. Background: Refractory wound is one of the most challenging clinical complications of diabetes mellitus. Studies have shown that PBMT can promote wound healing in many ways. Methods: We reported a 55-year-old male patient with refractory diabetic wound after secretory carcinoma of the parotid gland surgery responding to 810 nm laser. Results: After PBMT, the refractory diabetic wound healed gradually without adverse events. During follow-up 5-years, the healed wound remained stable and showed no signs of recurrence. Conclusions: PBMT can be potentially considered as a therapeutic method in diabetic patients with refractory diabetic wound.

Clinico-pathological factors associated with radioiodine refractory differentiated thyroid carcinoma status.

PURPOSE: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score. METHODS: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden's statistic. RESULTS: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95. CONCLUSION: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Nursing Considerations for Cytokine Release Syndrome in Relapsed/Refractory Multiple Myeloma: Experience with Teclistamab from the MajesTEC-1 Study.

OBJECTIVES: Cytokine release syndrome (CRS) is a systemic inflammatory response that is commonly observed as a class effect of T-cell-redirecting therapies. This article provides important practical guidance for nurses relating to the diagnosis, monitoring, and management of CRS in patients receiving teclistamab, based on experience from the MajesTEC-1 clinical trial and real-life nursing practice. METHODS: MajesTEC-1 is a phase 1/2 study of teclistamab in heavily pretreated patients with relapsed/refractory multiple myeloma. To mitigate the risk of high-grade CRS, patients were carefully monitored for early signs and symptoms of CRS (including fever, which must have fully resolved before teclistamab administration). RESULTS: A survey of nurses from several of the study sites provided additional real-life insights into nursing best practices for managing CRS from four academic institutions in three countries. CONCLUSIONS: In MajesTEC-1, 72% of patients treated with teclistamab experienced CRS, the majority of which was low grade. All cases resolved and none led to treatment discontinuation. Real-life supportive measures for CRS are generally aligned with those outlined in the study. IMPLICATIONS FOR NURSING PRACTICE: Because nurses are on the frontline of patient care, they play a crucial role in promptly recognizing the signs and symptoms of CRS and responding with timely and appropriate supportive treatment. This review provides important practical guidance for nurses on diagnosis, monitoring, and management of CRS in patients receiving teclistamab, based on experience from the MajesTEC-1 trial and real-life nursing practice.

Multimodal Approach for the Treatment of Complex Hypothalamic Hamartomas.

Hypothalamic hamartomas (HHs) are rare congenital lesions formed by heterotopic neuronal and glial cells attached to the mammillary bodies, tuber cinereum, and hypothalamus.They often present with an intractable epilepsy typically characterized by gelastic seizures but commonly associated with other types of refractory seizures. The clinical course is progressive in most of the cases, starting with gelastic seizures in infancy and deteriorating into complex seizure disorders that result in catastrophic epilepsy associated with cognitive decline and behavioral disturbances.Hamartomas are known to be intrinsically epileptogenic and the site of origin for the gelastic seizures. As antiepileptic drugs are typically ineffective in controlling HH-related epilepsy, different surgical options have been proposed as a treatment to achieve seizure control. Resection or complete disconnection of the hamartoma from the mammillothalamic tract has proved to achieve a long-lasting control of the epileptic syndrome.Usually, symptoms and their severity are typically related to the size, localization, and type of attachment. Precocious puberty appears mostly in the pedunculated type, while epileptic syndrome and behavioral decline are frequently related to the sessile type. For this reason, different classifications of HHs have been developed based on their size, extension, and type of attachment to the hypothalamus.The bigger and more complex hypothalamic hamartomas typically present with severe refractory epilepsy, behavioral disturbances, and progressive cognitive decline posing a formidable challenge for the control of these symptoms.We present here our experience with the multimodal treatment for complex hypothalamic hamartomas. After an in-depth review of the literature, we systematize our approach for the different types of hypothalamic hamartomas.

Successful treatment of paediatric refractory Hodgkin lymphoma with immunotherapy - A case report and literature review.

AIM: To describe a rare case of primary refractory Hodgkin lymphoma nodular sclerosis syncytial variant in a child and review immunotherapy in relapsed/refractory Hodgkin lymphoma. METHODS: We described the treatment course of a child with primary refractory classic Hodgkin lymphoma and discussed different options for salvage therapy, with an emphasis on immunotherapy. We searched PubMed for all published clinical trials investigating immunotherapy in classic Hodgkin lymphoma written in English until 31 June, 2023. The reference list of each identified paper was searched for additional publications. RESULTS: Our patient was salvaged with anti-programmed cell death 1 (PD-1) antibody therapy followed by high-dose chemotherapy with autologous stem cell rescue. Radiotherapy was avoided. We identified five one-armed phase II trials investigating anti-PD-1 therapy in first relapse/refractory disease in a total of 254 patients aged 9-71 years, of which one included 31 children. The complete remission rate before high-dose chemotherapy was 59%-95% overall and 67%-89% among those with refractory disease. CONCLUSION: Although it remains to be proven in randomised trials, anti-PD-1 therapy may provide higher complete response rates than traditional chemotherapy. Anti-PD-1 therapy has the potential to increase the chance of cure while decreasing the risk of late effects from chemotherapy and radiotherapy.

Cost-effectiveness of rimegepant oral lyophilisate compared to best supportive care for the acute treatment of migraine in the UK.

AIMS: Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and vomiting. Rimegepant 75mg, an oral lyophilisate calcitonin gene-related peptide antagonist, is the first treatment approved for both the acute and preventative treatment of migraine, and the first acute therapy approved in over 20-years. The objective was to assess the cost-utility of rimegepant compared with best supportive care (BSC) in the UK, for the acute treatment of migraine in the adults with inadequate symptom relief after taking at least 2 triptans, or for whom triptans are contraindicated or not tolerated. MATERIALS AND METHODS: A de novo model was developed to estimate incremental costs and quality-adjusted life years (QALYs), structured as a decision tree followed by Markov model. Patients received rimegepant or BSC for a migraine attack and were assessed for response (pain relief at 2-hours). Responders and non-responders followed different pain trajectories over 48-hour cycles. Non-responders discontinued treatment while responders continued treatment for subsequent attacks, with a proportion discontinuing over time. Data sources included a post-hoc pooled analysis of the phase 3 acute rimegepant trials (NCT03235479, NCT03237845, NCT03461757), and a long-term safety study (NCT03266588). The analysis was conducted from the perspective of the UK National Health Service and Personal Social Services over a 20-year time horizon. RESULTS: Rimegepant resulted in an incremental cost-utility ratio (ICUR) of £10,309 per QALY gained vs BSC, which is cost-effectiveness at a willingness to pay threshold of £30,000/QALY. Rimegepant generated +0.44 incremental QALYs and higher incremental lifetime costs (£4,492). Improved QALYs for rimegepant were a result of less time spent with severe and moderate headache pain. CONCLUSION: This study highlights the economic value of rimegepant which was found to be cost-effective for the acute treatment of migraine in adults unsuitable for triptans.

Hyperbaric Oxygen Enabled a Transition to Oral Steroids in an Acute Severe Ulcerative Colitis Flare.

Background: Ulcerative colitis (UC) is characterized in part by a dysregulated response to tissue hypoxia. While intravenous (IV) steroids are the mainstay of treatment for acute severe UC (ASUC), up to one-third of patients are refractory to steroids alone and require rescue therapy. Case Description: A 71-year-old female with extensive UC on infliximab presented with abdominal pain and more than 10 bloody bowel movements per day. Her infliximab concentration was undetectable with a positive antibody level. Flexible sigmoidoscopy on hospital day (HD)1 showed Mayo 3 colitis; biopsies for CMV were negative. She was started on hydrocortisone IV with improvement in her CRP from 56 to 40 mg/L. She also received 1 dose of vedolizumab. Hyperbaric treatments were offered but declined. By HD5, she was clinically improved, with a CRP of 9 mg/L. She was transitioned from IV to oral steroids. After starting oral steroids her symptoms relapsed, her CRP increased from 9 to 48 mg/L, and IV steroids were reinitiated on HD6. Hyperbaric medicine was reconsulted and she completed 5 hyperbaric oxygen (HBO2) treatments (HD 7-11) with prompt reduction in CRP, stool frequency, and bleeding. After 3 HBO2 treatments, she transitioned successfully from IV to oral steroids on HD9. Conclusions: This case demonstrates the potential of HBO2 therapy to help UC patients transition successfully from IV to oral steroids who were previously refractory to de-escalation. HBO2 therapy may be considered as an adjunctive treatment for patients with ASUC to potentiate the effects of standard therapies and avoid progression to colectomy.

Obesity attenuates the beneficial effect of an intrauterine infusion of autologous platelet-rich plasma during in vitro fertilization.

OBJECTIVE: To assess how obesity, normal weight (NW) versus overweight/obese (OW/OB), impacts platelet-rich plasma's (PRP) effectiveness during in vitro fertilization and how obesity affects platelets during the menstrual cycle. METHODS: Endometrial mean thickness (EMT), embryo implantation, and clinical pregnancy were assessed using a self-controlled retrospective study that enrolled 59 patients with two failed cycles and treated with autologous PRP (three-dose scheme). The NHANES dataset was used to assess platelet changes during the menstrual cycle, using the mean platelet volume to platelet count ratio (MPR) index. The COSINOR packages for R were used to determine rhythmicity. RESULTS: PRP treatments significantly improved the EMT (2.5 ± 1.4 mm, P<0.001), unaffected by obesity. After the PRP treatment, one patient spontaneously became pregnant; therefore, 58 patients underwent embryo transfer (62 cycles), of which in 39 cycles the embryos implanted (63.9%). This was a significant improvement from their previous cycle (vs. 22.6%, P<0.001). Clinical pregnancy also improved with the PRP treatment over the previous cycle (57.4% vs. 16.1%, P<0.001). When stratified by obesity, there was an appreciable decrease in embryo implantation and clinical pregnancy rates for the OW/OB group; nevertheless, the PRP treatment significantly improved embryo implantation and clinical pregnancy (P<0.05). A rhythm was observed with the MPR index (P<0.05) only for the NW group, suggesting that the platelets normally fluctuate during the menstrual cycle. CONCLUSION: PRP improved embryo implantation and clinical pregnancy rates; however, these beneficial effects were attenuated by obesity. PRP presumptively promoted a change in the uterine environment to mimic the normal findings associated with normal-weight women.

Fabrication of Layered SiC/C/Si/MeSi2/Me Ceramic-Metal Composites via Liquid Silicon Infiltration of Metal-Carbon Matrices.

The growing demand for composite materials capable of enduring prolonged loads in high-temperature and aggressive environments presents pressing challenges for materials scientists. Ceramic materials composed of silicon carbide largely possess high mechanical strength at a relatively low density, even at elevated temperatures. However, they are inherently brittle in nature, leading to concerns about their ability to fracture. The primary objective of this study was to develop a novel technique for fabricating layered composite materials by incorporating SiC-based ceramics, refractory metals, and their silicides as integral constituents. These layered composites were produced through the liquid-phase siliconization method applied to metal-carbon blanks. Analysis of the microstructure of the resultant materials revealed that when a metal element interacts with molten silicon, it leads to the formation of a layer of metal silicide on the metal's surface. Furthermore, three-point bending tests exhibited an enhancement in the bending strength of the layered composite in comparison to the base silicon carbide ceramics. Additionally, the samples demonstrated a quasi-plastic nature during the process of destruction.

Real-world patient characteristics, treatment patterns, and treatment outcomes of patients with diffuse large B-cell lymphoma by line of therapy.

BACKGROUND: Although initial treatment of diffuse large B-cell lymphoma (DLBCL) with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) can be effective, up to 50% of patients will develop refractory or relapsed (R/R) disease. This study aimed to provide contemporary data on characteristics, treatment patterns, and outcomes for R/R-DLBCL. METHODS: Patients with incident (January 2016 to March 2021) DLBCL age ≥18 years who initiated first-line (1L) therapy were identified from the COTA real-world database. Baseline characteristics, treatment patterns, and real-world outcomes, including time to next treatment (rwTTNT) and overall survival (rwOS), were assessed for the study population and by line of therapy (LOT). RESULTS: A total of 1347 eligible DLBCL patients were identified. Of these, 340 (25.2%) proceeded to receive 2L, of whom 141 (41.5%) proceeded to receive 3L, of whom 51 (36.2%) proceeded to receive 4L+. Most common treatments were R-CHOP in 1L (63.6%), stem cell transplant (SCT) in 2L (17.9%), polatuzumab vedotin, bendamustine, and rituximab (Pola-BR) in 3L (9.9%), and chimeric antigen receptor T-cell therapy (CAR-T) in 4L (11.8%). Treatment patterns were more variable in later LOTs. One- and 3-year rwOS from 1L initiation were 88.5% and 78.4%, respectively. Patients who received later LOTs experienced numerically lower 1- and 3-year rwOS (from 2L initiation: 62.4% and 46.4%, respectively). CONCLUSIONS: In this real-world analysis, 25.2% of patients experienced R/R-DLBCL after 1L with poor outcomes. Given the findings of this study, there is a high unmet need for novel, safe, and effective treatment options for patients with R/R DLBCL.

Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment: A phase 2 clinical trial (BG01-1801).

Background: Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC. Methods: Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m2 via intravenous injection daily, day 1-5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4-26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%-34.9%) in the intention-to-treat (ITT) cohort (N = 26) and 19.0% (95% CI, 5.4%-41.9%) in the per-protocol (PP) cohort (N = 21). The disease control rate was 69.2% (95% CI, 48.2%-85.7%) and 81.0% (95% CI, 58.1%-94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1-5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50-5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50-9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%-84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications. Conclusions: In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment. Trial registration: No.NCT03693547; https://classic.clinicaltrials.gov.

Mind the Gap: Paramedian approach for coccygectomy.

BACKGROUND CONTEXT: Coccydynia is pain in the coccyx that typically occurs idiopathically or from trauma. Most forms are self-limiting. However, if symptoms persist, non-surgical treatment options can include offloading, NSAIDs, physical therapy, and steroid injections. If all treatment options fail, a growing body of evidence supports a coccygectomy for symptomatic relief. The standard approach for a coccygectomy involves a midline incision cephalad to the anus along the gluteal cleft. Historically, this method has had high rates of infection. PURPOSE: To improve healing and decrease infection rate, we propose the paramedian approach to a coccygectomy. This approach has the benefit of distancing the surgical site from the anus, diminishing the crevice effect of the incision, and increasing the dermal and subdermal thickness for improved surgical closure. STUDY DESIGN/SETTING: We present a case series study of 41 patients who underwent the paramedian approach coccygectomy using a 4-6 cm incision, approximately 0.5-1.5 cm lateral to the midline, for coccyx removal. These patients were evaluated post-operatively to determine infection rate and various outcome measures. PATIENT SAMPLE: 41 patients suffering from refractory coccydynia had a coccygectomy via the paramedian approach between 2011 and 2022 by the senior author. OUTCOME MEASURES: Outcome measures included self-reported measures (Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) pain scale and satisfaction with procedure), physiologic measures (presence of infection and treatment provided) and functional measures (return to vocation/avocation) METHODS: Data was compiled and transferred to Microsoft Excel and analyzed. Two-tailed T-tests were used to compare the patient improvement in VAS and ODI as appropriate for statistical analysis. RESULTS: The patients' average age was 45.8 years. Patients' average body mass index was 27.9, with 71% of patients overweight or obese. 68% of patients were female. Trauma was the most common precipitating factor (75.6%). Five patients presented with post-operative complications (12.1%), one requiring an incision and drainage, and four others were treated with antibiotics for wound erythema. Post-operative evaluations showed continual improvement, with the most significant improvement reported greater than one-year post-operatively. The Visual Analogue Scale for pain dropped from 7.5 to 2.3 (P<0.001), and the Oswestry Disability Index improved from 30.1 to 9.6 (P<0.001). 86.7% percent of patients reported either a good or excellent result. CONCLUSION: Coccygectomies via the midline approach have a variable infection rate, likely due to proximity of the incision to the anus and due to the crevice effect of the gluteal cleft in terms of aeration. These contributing factors are overcome in the paramedian approach, making it an effective option for treating refractory coccydynia that is non-responsive to conservative management.