Left Margin Research Articles

Neonatal ventricular assist device implantation for high-risk hypoplastic left heart syndrome: How we do it.

Neonatal ventricular assist device implantation for high-risk hypoplastic left heart syndrome: How we do it.

Abstract CT541: Efficacy and safety of parsaclisib-ruxolitinib combination therapy in myelofibrosis patients (Pts) with low vs higher baseline platelet count (PC): A subgroup analysis of data from a phase 2 study

Abstract Background: Myelofibrosis (MF) pts often exhibit suboptimal response to chronic ruxolitinib therapy, possibly due to persistent PI3K pathway activation. In the ongoing phase 2 INCB 50465-201 trial (NCT02718300), add on parsaclisib (potent, highly selective PI3Kδ inhibitor) is showing preliminary efficacy in MF pts with suboptimal ruxolitinib response. JAK inhibitors (eg, ruxolitinib), are associated with thrombocytopenia; therefore, pts with low PC are commonly more difficult to treat. We present a subgroup analysis of efficacy and safety data from INCB 50465-201 by baseline PC. Methods: Eligible adults had primary/secondary MF with suboptimal response (palpable spleen >10 cm below left subcostal margin [LSM]; or palpable spleen 5-10 cm below LSM and active symptoms) after ≥6 months of ruxolitinib monotherapy (5-25 mg BID; stable dose ≥8 wks). Pts remained on their last stable ruxolitinib dose and received add on parsaclisib (10 or 20 mg QD for 8 wks; same dose QW thereafter) or parsaclisib (5 or 20 mg QD for 8 wks; 5 mg QD thereafter). For this analysis, spleen volume (SV), total symptom score (TSS) assessed by Myelofibrosis-Symptoms Assessment Form (MFSAF) v3.0 daily diary, and safety, were evaluated by baseline PC (low PC, 50-<100 × 109/L; higher PC, ≥100 × 109/L). Results: At data cutoff (8/27/2020), 67 pts were enrolled (low PC, n=21; higher PC, n=46; median age 68 y). For low vs higher PC, median prior duration of ruxolitinib use was 34.7 vs 14.9 months; baseline symptoms were worse for low PC vs higher PC (median [range] MFSAF-TSS, 21.4 [0.6-47] vs 10 [0-43]). For low vs higher PC, 9/18 (50.0%) vs 15/38 (39.4%) pts had SV reduction (SVR) ≥10% at wk 12; percentages of pts with SVR ≥10% were similar at wk 24 (6/17 [35.2%] vs 13/35 [37.1%]); 0 vs 1 pt had SVR ≥35% at wk 12; 2 vs 1 pt had SVR ≥35% at wk 24. Of pts with ≥10% SVR at wk 24, 4/6 with low PC and 9/13 with higher PC were on all daily dosing regimens. For low vs higher PC, median (range) percentage change in MFSAF-TSS was −20.5 (−56.6 to +17.1) vs −22.2 (−100 to +500) at wk 12; −26.1 (−54.7 to +2.4) vs −23.1 (−91.3 to +222.5) at wk 24. In both subgroups, nonhematologic treatment-emergent adverse events (TEAEs) were mostly grade 1/2. Most common (≥20%) TEAEs were dyspnea (33%), falls (33%), peripheral edema (29%), and nasal congestion (24%) for low PC; diarrhea (28%), nausea (24%), abdominal pain (24%), cough (20%), and fatigue (20%) for higher PC. For low vs higher PC, 9/21 (43%) vs 3/46 (7%) pts had parsaclisib dose interruption due to thrombocytopenia; 1 pt with low PC had ruxolitinib interruption due to thrombocytopenia. Conclusion: Add-on parsaclisib showed efficacy in pts from both low and higher baseline PC groups. Given the acceptable safety profile and efficacy of add-on parsaclasib, MF pts with both low and higher PC may be able to benefit from parsaclisib-ruxolitinib combination therapy. Citation Format: Abdulraheem Yacoub, Uma Borate, Raajit Rampal, Haris Ali, Eunice Wang, Aaron Gerds, Gabriela Hobbs, Marina Kremyanskaya, Elliott Winton, Casey O’Connell, Swati Goel, Stephen Oh, Gary Schiller, Albert Assad, Sue Erickson-Viitanen, Feng Zhou, Naval Daver. Efficacy and safety of parsaclisib-ruxolitinib combination therapy in myelofibrosis patients (Pts) with low vs higher baseline platelet count (PC): A subgroup analysis of data from a phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT541.

On the spectrum of some Bloch–Torrey vector operators

We consider the Bloch-Torrey operator in $L^2(I,{\mathbb R}^3)$ where $I\subseteq{\mathbb R}$. In contrast with the $L^2(I,{\mathbb R}^2)$ (as well as the $L^2({\mathbb R}^k,{\mathbb R}^2)$) case considered in previous works. We obtain that ${\mathbb R}_+$ is in the continuous spectrum for $I={\mathbb R}$ as well as discrete spectrum outside the real line. For a finite interval we find the left margin of the spectrum. In addition, we prove that the Bloch-Torrey operator must have an essential spectrum for a rather general setup in ${\mathbb R}^k$, and find an effective description for its domain.

Myeloproliferative neoplasms – a global view

Myeloproliferative neoplasms – a global view

Analysis of factors that influence the occurrence of erosive branches on the left margin of a urban gully in Bauru/SP: case of COHAB-16 / Análise de fatores que influenciam a ocorrência de ramificações erosivas à margem esquerda de uma boçoroca urbana em Bauru/SP: caso COHAB-16

The intense and accelerated urbanization process leads to an increase in the use and occupation of land in cities, resulting in a reduction in permeable areas, responsible for the infiltration of water into the soil. With the addition of impermeable areas, there is an increase in surface runoff which, when concentrated, especially in regions susceptible to erosion, favors the development of linear water erosion. The objective of the work presented here was to carry out a case study at the Edson Francisco da Silva Housing Nucleus, in the city of Bauru/SP to quantify the portion of surface runoff, caused by a predetermined period of precipitation, which influences the emergence and development of erosive features on the left margin of the gully in the study area. For this, the contribution area, the slope length and the average slope were determined by Google Earth software, and the calculation of runoff was performed using the Rational Method. The survey of features, analysis and quantification of the drain inlets and study of the surroundings were carried out through field visits. In order to quantify the benefit that compensatory urban drainage techniques would bring in reducing the flow that reaches the conventional drainage system present in the neighborhood, the micro reservoir and the infiltration trench were studied.

Percutaneous Radiologic Gastrostomy in Patients After Partial Gastrectomy: A Retrospective Study to Assess the Technical Feasibility of Postsurgical Remnant Stomach Access.

To evaluate the technical feasibility of percutaneous radiologic gastrostomy in patients after partial gastrectomy. This retrospective study included 15 consecutive gastrectomized patients with attempted percutaneous radiologic gastrostomy at our institution between April 2014 and March 2021. When the stomach was sufficiently insufflated to distend below the left anterior subcostal margin, percutaneous radiologic gastrostomy with gastropexy was conventionally performed by the Seldinger technique. When the stomach was still highly positioned and/or overlaid by the other organs, some adjunctive maneuvers, such as hydro-displacement, intragastric balloon support, or cephalad oblique puncture or left intercostal puncture, were employed as modified gastrostomy. Ultrasonography or x-ray or computed tomography fluoroscopy was used for imaging guidance during the gastric puncture. Adequate tube placement was defined as technical success. Technical details, clinical outcomes, and complications were reviewed. One patient underwent percutaneous radiologic jejunostomy instead of gastrostomy because safe gastric access could not be ensured. Seven patients underwent conventional gastrostomy; the other seven underwent modified gastrostomy with no gastropexy. The technical success rate was 100% (7/7) in the conventional group and 85.7% (6/7) in the modified group. The stomach was punctured under x-ray or computed tomography fluoroscopy for conventional gastrostomy. In contrast, the combination of various modalities was used for modified gastrostomy except for one failed case with unintentional transhepatic access. During a median follow-up of 108days, no major complications occurred. The adequate combination of multimodal imaging guidance and technical modifications could secure radiological creation of gastrostomy for the postsurgical stomach. Level 4, Case Series.

Mary of Burgundy Alive or Dead

Three depictions of Mary of Burgundy seated on horseback were made soon after the duchess’s death.The drawn copy of a lost work by Hugo van der goes commemorates the negotiations held in Trier in 1473 between frederick iii and Charles the Bold, when they made their first agreement on joining their children in marriage. The composition is strikingly reminiscent of the theme of The Meeting of the Three Living and the Three Dead; the high-born female rider arriving behind Maximilian is Mary of Burgundy, depicted after her death. The man confronting the riders with their mortality probably refers to Charles the Bold (d. 1477). The original work was likely to have been commissioned by Maximilian sometime between the death of the duchess and that of the painter, that is between March and December 1482.Like the drawing, the allegorical poem completed in 1483 by olivier de La Marche is a commemoration of the recently deceased dukes and duchess of the House of Burgundy. for the edition of the poem published by the Brethren of the Common Life in gouda, the drawing associated with Hugo van der goes was utilised to illustrate the chapter on the death of Mary of Burgundy.The protagonist of The Meeting of the Three Living and the Three Dead in the manuscript known as the “Berlin Hours of Mary of Burgundy and Maximilian of Austria” is Mary of Burgundy, who died in a riding accident. i refute all the arguments suggesting that the miniature preceded the duchess’s death. The double letters “M” on the harness of Mary’s horse (which are also found several other times in the book of hours) refer not only to the names of the ducal couple, but also to words associated with death. The miniature itself was probably commissioned by Maximilian, after his wife’s death. With its softer brushwork, the decorative frame around the miniature – as well as the entire recto of folio 221 – was probably made when the manuscript was in the possession of Margaret of Austria. The personification of Death differs from the verso in many respects (scale, background, style); iconographically it can be considered an afterthought. The green parrot and golden dove in the left margin are also afterthoughts. The two birds appear in the Épîtres de l’Amant vert (1505), the consolatory poem composed for Margaret by Jean Lemaire: one bird was the mother’s favourite, the other her daughter’s favourite; both ended their lives in the mouths of dogs (which had been barking on the verso of folio 220 for a few years before). Here and now, in the margin of the recto of folio 221, the birds representing the souls of mother and daughter are inhabitants of Paradise. The protagonist in the verso of folio 158 of the London rothschild Hours – the image is a copy of the Berlin Meeting – is the commissioner of the manuscript, and also the owner of the Berlin manuscript: Margaret of Austria, identifying with and commemorating her mother Mary of Burgundy. The depiction facing it in the recto of folio 159 alludes to the series of events (the two funerals) that followed the death of Margaret’s husband, Philibert ii, with a proleptic depiction of st. nicolas’s Church in Brou (their future common tomb). Besides the riding ladies, the illustrations of the office of the Dead in the Berlin and London Hours share numerous similarities.

A Father's Guide to the Pulitzer Gallery

A Father's Guide to the Pulitzer Gallery Jefferson Slagle (bio) Two figures stand in a low, dark hallway. On the wall ahead of them a photo is illuminated: a man in a long-sleeved T-shirt emblazoned with the American flag, his face curtained in dreadlocks, a bag of St. Louis Red Hot Riplets in one hand, a flaming tear gas can in the other. His arm unfurls behind him, primed to hurl the spangled canister back at a police officer who stands, they infer, just outside the frame. They've seen this photo before, but never at this size, so close and so large it obscures everything behind it. The exhibit hall occupies the basement of a university art museum, and the figures are a father and daughter taking a tour of the campus, but you know this from looking at them. A year from now, the college she chooses will be her home, the first of her own making. He will be the guest, she the proud host showing off the historic building where her international politics class meets, the trail where she runs in the evenings, the sculptures on the quad. But today they defer to each other in the uncharted space of her anticipated departure, circling in a tentative, fleeting orbit. On the far side of the entrance wall is a placard, a quote from Pulitzer-winning photographer Eddie Adams: "If it makes you laugh, if it makes you cry, if it rips out your heart, it's a good picture." They consider this message and turn away from it, toward the gallery. She heads right, toward the newer photos. He goes left, into the past. On the wall behind them, the world is about to burn. [End Page 103] ________ On the wall before him, Air Force Colonel Robert Storm is returning home. His dark, dress-uniformed back anchors the left margin of the photo. His family runs toward him out of the right side of the frame, his wife and young son trailing, a daughter and older son ahead of them. His oldest daughter, closest to him, has taken flight, her arms thrown out like wings to embrace him, heedless with joy. The caption informs the viewer that his wife has filed for divorce, and a few weeks later they will separate for good. Their children, at this moment, are unaware of the upheaval that awaits them just outside the frame. The conceit of the Pulitzer exhibit is to make each photo play a single narrative beat in a history of the modern world, to build a narrative out of images. It's the kind of activity our brains are designed to perform, making connections among apparently disconnected things, then connecting those things to us. John Berger observes that "we never look at just one thing; we are always looking at the relation between things and ourselves. Our vision is continually active, continually moving, continually holding things in a circle around itself, constituting what is present to us as we are." What synaptic connections are firing in the heads of these giddy, oblivious running children, in the slower, time-snarled heads of their equivocal parents? What fireworks erupt inside the head of the daughter, across the room, as she watches a pair of Syrian rebels huddle in a sniper's nest, the sun flaring through bullet holes behind them, each beam diverging from the others inside that cramped, dim space? It seems ridiculous to treat these photos, this room, as a kind of historical narrative, to make each bear the weight and complexity of its birth year and the effects that will flow out of it. Nineteen seventy-four was not only the year Col. Storm returned home; it was also the year Patty Hearst was kidnapped, the year Muhammad Ali knocked out George Foreman at the Rumble in the Jungle, the year the Milgram experiment was first described, Ted Bundy abducted two women in Washington state and one woman escaped him in Salt Lake City, the second-largest swarm of tornadoes in U.S. history struck thirteen states, Notre Dame upset UCLA to end a record eighty-eight-game men's basketball...

English

A 15-year-old female patient came with complaint of pain in the left hypochondriac region from past 2 months, which was dull aching, intermittent, aggravated on taking deep breaths, and relieved at rest. Patient also gave history of early satiety. No history of trauma, vomiting, altered bowel habits, fever, night sweats, and weight loss. The patient denied history of any recent travel. On physical examination, a firm nontender mass of size 20×15 cm was palpated in the left hypochondriac region extending to the epigastric, umbilical and left lumbar region with medial border at 5cm right lateral to the umbilicus and finger insinuation was not possible below the left costal margin. The patient underwent ultrasound abdomen which showed large well defined cystic lesion measuring 20X19X30cm, volume 5000-5700cc occupying the left hypochondrium, lumbar, epigastric and umbilical regions with irregular trabeculated wall and internal echoes within. It was seen causing mass effect in the form of posterior displacement of bilateral kidneys, spleen and inferior displacement of bowel loops. Features were suggestive of probable large mesenteric cyst. Computed tomography (CT) of abdomen and pelvis with oral and intravenous contrast was done which showed a large thin-walled abdominal cystic lesion measuring 19x18x22cm of volume approximately 3500- 4000cc occupying the left hypochondrium, epigastric region, umbilical region, reaching up to the lumbar region. It was seen arising from spleen with thinned out splenic parenchyma along its superior, lateral and inferior aspect (claw sign). Anteriorly it was extending to the anterior abdominal wall and abutting the recti muscles. Mass effect was noted on liver and right kidney with displacement of the organs (Figure 1: a, b).

Initial entry via the left upper quadrant with an optical trocar in laparoscopic bariatric surgery.

Laparoscopic bariatric surgery (BS) is not readily performed in Japan. To facilitate safe initial access to the abdominal cavity, we insert an optical viewing trocar at a unique site in the left upper quadrant (LUQ). Herein, we describe the technique, its advantages, and outcomes. Briefly, the optical trocar is inserted just below the left subcostal margin, 8cm from the midline. On insertion, layers of the abdominal wall are visualized on the monitor. Depending on the angle of insertion, five, seven, or eight layers are seen. In assessing our initial entry technique, used in 21 obese patients undergoing laparoscopic sleeve gastrectomy, we found median insertion time to be 25 seconds. There were no related complications. In nearly all (20/21) patients, the abdominal wall was visualized as seven layers: subcutaneous fat, anterior rectus sheath, rectus abdominis muscle, posterior rectus sheath, transverse abdominis muscle, transversalis fascia, and peritoneum. Understanding the layers of the abdominal wall visualized during optical trocar insertion in the LUQ will provide for safe and rapid initial entry in patients undergoing laparoscopic BS and can further the widespread acceptance of laparoscopic BS.

Empirical and semi-empirical chlorophyll-a modeling for water quality assessment through river-lake transition in extreme Southern Brazil.

Mirim lagoon is the second largest lacustrine water body in Southern Brazil, providing water for local communities. However, algae growth and water quality in the lagoon and in tributaries rivers is influenced by nutrient's increase. In this context, this study performs the empirical and semi-empirical chlorophyll-a (Chl-a) modeling using remote sensing and in situ data for water quality assessment. Water quality data were collected at 15 sample locations in the lagoon on the date of Sentinel-2 satellite overpass. Surface reflectance data were derived from the Sen2Cor atmospheric correction method and correlated with Chl-a concentration. The best model presented a Pearson's correlation coefficient = 0.81 and Mean Absolute Error = 0.13µg.L-1. Low Chl-a concentration is observed at the Northern lagoon, possibly due to suspended solids presence. The same occurs in the left margin, being associated with the influence of land use for agriculture. High Chl-a concentrations are associated with shallower and lentic areas. The mean Chl-a concentration predicted by the model was 17.34μg.L-1, similar to the observed value in situ (16.32μg.L-1). Overall, the empirical model developed can be applied as a tool to reduce costs and efforts in fieldwork measures and to understand eutrophication in this river-lake transition ecosystem.

O projeto educacional da Itaipu Binacional para a margem direita paraguaia (1974-1985)

This article analyzes the "Itaipu Binational Educational Project for the paraguayan right Margin", made possible during the construction period of the Itaipu Binational Hydroelectric Power Plant between 1974 and 1985m. On the right bank, Paraguay organized an ideological structure that was based on formal and non-formal education initiatives, made possible in the Housing Villages and Construction Site. Under the assumptions of historical-dialectical materialism, this research used theoretical, bibliographic, documentary and semi-structured interviews. It was concluded that, although the control and consensus-building strategies were similar to those used in the Brazilian left margin, in Paraguay there was greater participation of the public power in the provision of formal education, through agreements between the entity and the "Ministry of Education and Cult - MEC ".

An unusual case of bone regeneration of a necrotic mandible with pathologic fracture in an elderly hemodialysis patient with medication-related osteonecrosis of the jaw: a case report and review of the\xa0literature

BackgroundBisphosphonates are frequently used for osteoporosis. Medication-related osteonecrosis of the jaw, a complication of bone-modifying agents, including bisphosphonates or angiogenic inhibitors, can be challenging to treat in elderly patients with numerous preexisting conditions. Achieving good treatment outcomes is especially difficult in patients with pathological fractures accompanied with extraoral fistulae.Case presentationWe report an unusual case of prominent bone regeneration following palliative surgical treatment in a 72-year-old Japanese female patient undergoing hemodialysis. She previously had severe osteoporosis due to renal osteodystrophy and was receiving antiresorptive intravenous bisphosphonate. Computed tomography revealed a discontinuous left lower mandibular margin with a pathologic fracture and extensive, morphologically irregular sequestrum formation (80 × 35 × 20 mm). The patient was diagnosed with stage III medication-related osteonecrosis of the jaw and pathologic mandibular fracture. Immediately before the surgery, the anticoagulant used for dialysis was changed from heparin to nafamostat mesylate to reduce the risk of intraoperative bleeding. Sequestrectomy was performed under general anesthesia. Postoperative infection was not observed, the intraoral and submandibular fistula disappeared, and, surprisingly, prominent spontaneous bone regeneration was observed postoperatively at 6 months. Despite the severe systemic condition of the patient, the conservative surgical approach with sequestrectomy has yielded desirable results for more than 6 years since the surgery.ConclusionsThis rare report of spontaneous bone regeneration in a patient of advanced age and poor general condition is the oldest case of mandibular regeneration ever reported.

Subgroup Analysis from a Phase 2 Study of the Efficacy and Safety of Parsaclisib, a Selective PI3Kδ Inhibitor, in Combination with Ruxolitinib in Patients with Myelofibrosis (MF)

Subgroup Analysis from a Phase 2 Study of the Efficacy and Safety of Parsaclisib, a Selective PI3Kδ Inhibitor, in Combination with Ruxolitinib in Patients with Myelofibrosis (MF)

Safety and Tolerability of Fedratinib (FEDR), an Oral Inhibitor of Janus Kinase 2 (JAK2), in Patients with Intermediate- or High-Risk Myelofibrosis (MF) Previously Treated with Ruxolitinib (RUX): Results from the Phase 3b FREEDOM Trial

Safety and Tolerability of Fedratinib (FEDR), an Oral Inhibitor of Janus Kinase 2 (JAK2), in Patients with Intermediate- or High-Risk Myelofibrosis (MF) Previously Treated with Ruxolitinib (RUX): Results from the Phase 3b FREEDOM Trial

Comparison of Methods to Estimate Splenic Volume in Myelofibrosis Trials

▪Primary myelofibrosis (PM) is a chronic blood cancer which increases burden on the spleen to produce blood cells and results in palpable splenomegaly. In the clinic, splenomegaly is classified based on the distance between the spleen's lowest point and the left costal margin, however, this method is highly subjective and depends on the subject's position and respiration. Imaging techniques have the potential to provide accurate, reliable, and reproducible measurements of splenic volume (SV). In clinical trials assessing therapy response, an accepted imaging-based endpoint is ≥35% reduction in SV at week 24 from baseline as measured by Magnetic Resonance Imaging (MRI) or Computer Tomography (CT). A ≥25% increase in SV is typically considered progression. The most accurate method for volume assessment is manual segmentation, since the entire spleen boundary can be utilized for the volume calculation. This study compared two other volume estimation methods: ellipsoid method and a model proposed by Bezerra et al (AJR Am J Roentgenol. 2005). We compared the methods' performance in assessing treatment response or progression based on SV change from baseline to week 24.Imaging data from 30 participants were used in this study, predominantly acquired using MRI modality; CT was used as an alternative, when MRI was contraindicated. Scans from two timepoints per participant were used: baseline and 24 weeks after start of treatment. For the manual segmentation method, preliminary regions of interest were manually outlined on every imaging slice by an experienced imaging analyst and then reviewed by a trained radiologist. SV was derived by multiplying the number of voxels contained in the spleen outlined by the voxel size of the scan. For the ellipsoid method, maximum width (W) and orthogonal thickness (T) were measured on the axial images. Length (L) was measured by multiplying the number of slices containing spleen by the slice interval. Ellipsoid volume was calculated as follows:V = W * T * L * π / 6For the length-estimated SV based on the Bezerra et al model, spleen length was utilized as shown:V = (L - 5.8006) / 0.0126For each of the three methods, percent change in SV was calculated from baseline to week 24. Pearson's correlation coefficient and Bland Altman analysis were implemented for comparison of methods to manual segmentation. Sensitivity and specificity analysis was performed to determine the accuracy of each method to predict response or progression.The manual segmentation volume was significantly correlated with both the ellipsoid method (r(58) = 0.94, p < 0.0001) and the length-estimated method (r(58) = 0.89, p < 0.0001). When assessing percent changes from baseline to week 24 using manual segmentation, 4 of the participants achieved splenic response and 4 progressed with 25% increase in SV. However, analysis using ellipsoid method yielded 3 responding and 2 progressing participants. Finally, analysis with length-estimated volume yielded no responding or progressing participants. This data is also illustrated in Table 1, which shows the sensitivity and specificity results. Figure 1 illustrates Bland-Altman plots, suggesting that ellipsoid method provides a more accurate estimation of the change in SV compared to length-estimated volume. Furthermore, we found that the inaccuracy with length-estimated volume increases with larger spleens (not shown).Change in spleen volume contributes to the primary/ secondary endpoints in large multi-center clinical trials for myelofibrosis, so it is imperative that the methods used to measure SV are consistent across imaging sites. The current standard for assessing SV is the manual segmentation method because it provides the most comprehensive measurement of spleen size however, this process is burdensome, time consuming, and requires specific training. The ellipsoid and length-estimated methods were strongly correlated with the manual segmentation method; however, they were not as sensitive when determining treatment response or progression. The length-estimated method had the least level of agreement with manual segmentation. The ellipsoid method may be a better alternative; however, it is important to use one method consistently across all visits for a study participant. Additional work is required to test performance of methods on a larger cohort, as well as assess automated segmentation algorithms that may reduce the burden of manual tracing. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Splenomegaly (SPML) in Polycythemia Vera (PV): Its Clinical Significance and Relation to Myelofibrosis and Survival

▪Introduction: SPML is considered a hallmark of PV, but its frequency, as reported in the literature, ranges from 20% to 75%. It has been assumed, without documentation, that SPML may be accompanied by symptoms and signs and may affect prognosis. Moreover, expensive radiographic tests have become mandatory in some recent phase 2 drug trials in PV (and ET) to carefully document spleen size on trial entry and its change, if any, during therapy. Because systematic studies have not been performed, we studied SPML in patients (pts) with PV at their initial diagnosis (DX) or at first presentation (PRES) at our institution, Weill Cornell Medicine (WCM), and determined its clinical significance.Methods: This single-center retrospective study was approved by the WCM institutional review board. A systematic literature search including PubMed, Embase, and Cochrane School relevant to the specific search questions was unrevealing. We used a research data repository based on an automated query system which had aggregated longitudinal clinical information pertaining to our PV patients for our analysis of spleen size (Abu-Zeinah et al. Leukemia 2021). Standardized PV diagnostic criteria were used for all pts (Silver et al. Blood 2013). As a tertiary referral center within a major metropolitan area, our PV population is composed of those diagnosed at WCM (DX) and those presenting to WCM some time after diagnosis (PRES). Degree of SPML was categorized into 3 subgroups: (1) <1 cm if the spleen was not enlarged, (2) palpable 1-5 cm, or (3) more than 5.0 cm below the left costal margin of the abdomen in the medial clavicular line in the supine or left lateral decubitus position; it was also considered enlarged after splenic ultrasound scan (US) based upon the method and verified formula of Chow KU, et al. Radiology 2016. Spleen size was correlated with age, sex, race, and ELN risk score, and symptoms including pruritus, night sweats, anorexia, abdominal discomfort and pain. Progression to myelofibrosis (MF) with myeloid metaplasia was defined per ELN/IWG-MRT criteria. Spleen measurements after progression to MF were excluded. Peripheral blood smears were routinely examined to view RBC morphology and to exclude leukoerythroblastosis. MF-free survival (MFS) and overall survival (OS) were calculated using the Kaplan-Meier log rank test among the various spleen subgroups. Multivariable survival analysis (MVA) was performed using a Cox proportional hazards model.Results: From our 470 PV dataset, 351 pts had documented spleen size at DX (165) or PRES (186). The median age for all patients was 60 years (yr), for DX 54 yr, for PRES 62 yr. The median DX ages of SPML <1 cm, 1-5 cm, and >5 cm were 56, 50, and 54 yr respectively (p=0.011). The median time between first evaluation for PV and first visit at WCM (PRES) was 2 years (range 0-30). 49% were female and 13% were non-white (Figure 1a). There was no correlation between spleen size and ELN risk scores. The linkage between SPML and symptoms will be reported. Overall survival of the three groups was similar at 12 years (Figure 1b). SPML at presentation, however, was associated with increased risk of MF (1-5cm versus 0: HR 2.56, p=0.026; >=5cm versus 0: HR 5.64, p<0.001), independent of age or disease duration in MVA.Discussion & Conclusion: Patients who had SPML > 5cm at presentation had a worse MFS than those with a lesser degree of SPML or no SPML (1-5 cm or <1 cm). For determining SPML, clinical examination and calculated US length were equally satisfactory. In the absence of clinical SPML, radiographic tests appear unnecessary. However, for SPML > 5cm, and unusual body types, more detailed radiographic studies may still be required. SPML was more common in younger patients, suggesting more aggressive disease and earlier progression to MF. ELN risk category did not correlate with SPML, suggesting an additional reason for its revision. Our PV patients with SPML > 5cm at DX or PRES did not have a decreased OS at 12 years, but did have a reduced MF-free survival. These data support the WHO mandated requirement for marrow biopsy for diagnosis of PV, especially for patients with SPML but also as a baseline requirement to establish the presence of MF less than grade 2. Patients with SPML> 5cm appear to be at high risk of MF progression and must be monitored closely for this event and treated appropriately. [Display omitted] DisclosuresSilver: Abbvie: Consultancy; PharamEssentia: Consultancy, Speakers Bureau. Scandura: CR&T (Foudation): Research Funding; European Leukemia net: Honoraria, Other: travel fees ; MPN-RF (Foundation): Research Funding; Constellation: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Abu-Zeinah: PharmaEssentia: Consultancy.

A Randomized, Phase 3 Trial of Fedratinib Versus Best Available Therapy in Patients with Intermediate-2 or High-Risk Myelofibrosis Previously Treated with Ruxolitinib (FREEDOM2)

A Randomized, Phase 3 Trial of Fedratinib Versus Best Available Therapy in Patients with Intermediate-2 or High-Risk Myelofibrosis Previously Treated with Ruxolitinib (FREEDOM2)

Spleen and Symptom Responses with Fedratinib (FEDR) in Patients with Myelofibrosis (MF) and Substantial Splenomegaly

Spleen and Symptom Responses with Fedratinib (FEDR) in Patients with Myelofibrosis (MF) and Substantial Splenomegaly

Tagraxofusp (SL-401) in Patients with Chronic Myelomonocytic Leukemia (CMML): Updated Results of an Ongoing Phase 1/2 Trial

Tagraxofusp (SL-401) in Patients with Chronic Myelomonocytic Leukemia (CMML): Updated Results of an Ongoing Phase 1/2 Trial