Early Retreat Research Articles

Modeling the timing of Patagonian Ice Sheet retreat in the Chilean Lake District from 22–10 ka

Abstract. Studying the retreat of the Patagonian Ice Sheet (PIS) during the last deglaciation represents an important opportunity to understand how ice sheets outside the polar regions have responded to deglacial changes in temperature and large-scale atmospheric circulation. At the northernmost extension of the PIS during the Last Glacial Maximum (LGM), the Chilean Lake District (CLD) was influenced by the southern westerly winds (SWW), which strongly modulated the hydrologic and heat budgets of the region. Despite progress in constraining the nature and timing of deglacial ice retreat across this area, considerable uncertainty in the glacial history still exists due to a lack of geologic constraints on past ice margin change. Where the glacial chronology is lacking, ice sheet models can provide important insight into our understanding of the characteristics and drivers of deglacial ice retreat. Here we apply the Ice Sheet and Sea-level System Model (ISSM) to simulate the LGM and last deglacial ice history of the PIS across the CLD at high spatial resolution (450 m). We present a transient simulation of ice margin change across the last deglaciation using climate inputs from the National Center for Atmospheric Research Community Climate System Model (CCSM3) Trace-21ka experiment. At the LGM, the simulated ice extent across the CLD agrees well with the most comprehensive reconstruction of PIS ice history (PATICE). Coincident with deglacial warming, ice retreat ensues after 19 ka, with large-scale ice retreat occurring across the CLD between 18 and 16.5 ka. By 17 ka, the northern portion of the CLD becomes ice free, and by 15 ka, ice only persists at high elevations as mountain glaciers and small ice caps. Our simulated ice history agrees well with PATICE for early deglacial ice retreat but diverges at and after 15 ka, where the geologic reconstruction suggests the persistence of an ice cap across the southern CLD until 10 ka. However, given the high uncertainty in the geologic reconstruction of the PIS across the CLD during the later deglaciation, this work emphasizes a need for improved geologic constraints on past ice margin change. While deglacial warming drove the ice retreat across this region, sensitivity tests reveal that modest variations in wintertime precipitation (∼10 %) can modulate the pacing of ice retreat by up to 2 ka, which has implications when comparing simulated outputs of ice margin change to geologic reconstructions. While we find that TraCE-21ka simulates large-scale changes in the SWW across the CLD that are consistent with regional paleoclimate reconstructions, the magnitude of the simulated precipitation changes is smaller than what is found in proxy records. From our sensitivity analysis, we can deduce that larger anomalies in precipitation, as found in paleoclimate proxies, may have had a large impact on modulating the magnitude and timing of deglacial ice retreat. This fact highlights an additional need for better constraints on the deglacial change in strength, position, and extent of the SWW as it relates to understanding the drivers of deglacial PIS behavior.

Abrupt Holocene ice loss due to thinning and ungrounding in the Weddell Sea Embayment

The extent of grounded ice and buttressing by the Ronne Ice Shelf, which provides resistance to the outflow of ice streams, moderate West Antarctic Ice Sheet stability. During the Last Glacial Maximum, the ice sheet advanced and was grounded near the Weddell Sea continental shelf break. The timing of subsequent ice sheet retreat and the relative roles of ice shelf buttressing and grounding line changes remain unresolved. Here we use an ice core record from grounded ice at Skytrain Ice Rise to constrain the timing and speed of early Holocene ice sheet retreat. Measured δ18O and total air content suggest that the surface elevation of Skytrain Ice Rise decreased by about 450 m between 8.2 and 8.0 kyr before 1950 ce (±0.13 kyr). We attribute this elevation change to dynamic thinning due to flow changes induced by the ungrounding of ice in the area. Ice core sodium concentrations suggest that the ice front of this ungrounded ice shelf then retreated about 270 km (±30 km) from 7.7 to 7.3 kyr before 1950 ce. These centennial-scale changes demonstrate how quickly ice mass can be lost from the West Antarctic Ice Sheet due to changes in grounded ice without extensive ice shelf calving. Our findings both support and temporally constrain ice sheet models that exhibit rapid ice loss in the Weddell Sea sector in the early Holocene.

Early Holocene ice retreat from Isle Royale in the Laurentian Great Lakes constrained with 10Be exposure-age dating

Abstract. The timing of the Laurentide Ice Sheet's final retreat from North America's Laurentian Great Lakes is relevant to understanding regional meltwater routing, changing proglacial lake levels, and lake-bottom stratigraphy following the Last Glacial Maximum. Recessional moraines on Isle Royale, the largest island in Lake Superior, have been mapped but not directly dated. Here, we use the mean of 10 new 10Be exposure ages of glacial erratics from two recessional moraines (10.1 ± 1.1 ka, one standard deviation; excluding one anomalously young sample) to constrain the timing of Isle Royale's final deglaciation. This 10Be age is consistent with existing minimum-limiting 14C ages of basal organic sediment from two inland lakes on Isle Royale, a sediment core in Lake Superior southwest of the island, and an estimated deglaciation age of the younger of two subaqueous moraines between Isle Royale and Michigan's Keweenaw Peninsula. Relationships between Isle Royale's landform ages and Lake Superior bottom stratigraphy allow us to delineate the retreat of the Laurentide ice margin across and through Lake Superior in the early Holocene. We suggest that Laurentide ice was in contact with the southern shorelines of Lake Superior later than previously thought.

Effect of global and regional SST biases on the East Asian Summer Monsoon in the MetUM GA7 and GC3 configurations

Climate-length experiments of the Met Office Unified Model Global Atmosphere 7.0 (GA7) and Global Coupled 3.0 (GC3) configurations are evaluated against observations and reanalyses for the simulation of the East Asian summer monsoon (EASM). The results show systematic model biases, such as overestimated rainfall over southern China and underestimated rainfall over northern China, suggesting a monsoon that does not penetrate northward enough. We evaluate the effects on the EASM of regional errors in sea-surface temperature (SST) conditions in three regions: the Pacific, the Indian, and the Atlantic Oceans. The global SST biases in GC3 configuration substantially shift the EASM seasonal cycle: a late northward progression of the EASM in the early/mid-monsoon season, and an early retreat of the monsoon that also reduces rainfall over most of northern China. The EASM seasonal rainfall bias in the EASM region is linked to changes in the locations and strength of the western North Pacific subtropical high, which is associated with biases in local evaporation and moisture transport towards South China. GC3 biases in the El Niño-Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD) teleconnection pathways also influence the EASM biases. GC3 biases weaken the ENSO teleconnection to the EASM and cause a strong dry bias in southeast China during developing El Niño.

Geologic controls on the genesis of the Arctic permafrost and sub-permafrost methane hydrate-bearing system in the Beaufort–Mackenzie Delta

The Canadian Mackenzie Delta exhibits a high volume of proven sub-permafrost gas hydrates that naturally trap a significant amount of deep-sourced thermogenic methane (CH4) at the Mallik site. The present study aims to validate the proposed Arctic sub-permafrost gas hydrate formation mechanism, implying that CH4-rich fluids were vertically transported from deep overpressurized zones via geologic fault systems and formed the present-day observed GH deposit since the Late Pleistocene. Given this hypothesis, the coastal permafrost began to form since the early Pleistocene sea-level retreat, steadily increasing in thickness until 1 Million years (Ma) ago. Data from well logs and 2D seismic profiles were digitized to establish the first field-scale static geologic 3D model of the Mallik site, and to comprehensively study the genesis of the permafrost and its associated GH system. The implemented 3D model considers the spatially heterogeneously distributed hydraulic properties of the individual lithologies at the Mallik site. Simulations using a proven thermo-hydro-chemical numerical framework were employed to gain insights into the hydrogeologic role of the regional fault systems in view of the CH4-rich fluid migration and the geologic controls on the spatial extent of the sub-permafrost GH accumulations during the past 1 Ma. For >87% of the Mallik well sections, the predicted permafrost thickness deviates from the observations by less than 0.8%, which validates the general model implementation. The simulated ice-bearing permafrost and GH interval thicknesses as well as sub-permafrost temperature profiles are consistent with the respective field observations, confirming our introduced hypothesis. The spatial distribution of GHs is a result of the comprehensive interaction between various processes, including the source-gas generation rate, subsurface temperature, and the hydraulic properties of the structural geologic features. Overall, the good agreement between simulations and observations demonstrates that the present study provides a valid representation of the geologic controls driving the complex permafrost-GH system. The model’s applicability for the prediction of GH deposits in permafrost settings in terms of their thicknesses and saturations can provide relevant contributions to future GH exploration and exploitation.

Cover Image

EcosphereVolume 14, Issue 3 e4119 COVER IMAGEOpen Access Cover Image First published: 06 March 2023 https://doi.org/10.1002/ecs2.4119AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract COVER PHOTO: Adélie penguins (Pygoscelis adeliae) have life histories dependent on suitable sea ice, landscape, seascape, and preyscape conditions—making them a valuable indicator of climate change and variability. Long-term patterns in ecosystem phenology were investigated from the perspective of Adélie penguins using data from the Palmer Antarctica Long Term Ecological Research (LTER) program. Cimino et al. (Ecosphere, Volume 14, Issue 2, Article e4417; doi: 10.1002/ecs2.4417) show that sea ice retreat and increasing photoperiod in the spring trigger a sequence of events from late spring into summer, including Adélie penguin clutch initiation, snow melt, calm weather, phytoplankton blooms, particulate organic carbon flux, peak whale abundances, and bacterial accumulation. Later sea ice retreat generally resulted in events happening later and the ecosystem was more “predictable” than early retreat years. The timing of the Adélie penguins breeding cycle was relatively consistent compared to other events, making them susceptible to mismatches in optimal environmental windows or prey characteristics that could ultimately influence chick survival. Photo credit: Darren Roberts Volume14, Issue3March 2023e4119 RelatedInformation

Characterizing coastal phytoplankton seasonal succession patterns on the West Antarctic Peninsula

AbstractIn coastal West Antarctic Peninsula (WAP) waters, large phytoplankton blooms in late austral spring fuel a highly productive marine ecosystem. However, WAP atmospheric and oceanic temperatures are rising, winter sea ice extent and duration are decreasing, and summer phytoplankton biomass in the northern WAP has decreased and shifted toward smaller cells. To better understand these relationships, an Imaging FlowCytobot was used to characterize seasonal (spring to autumn) phytoplankton community composition and cell size during a low (2017–2018) and high (2018–2019) chlorophyll a year in relation to physical drivers (e.g., sea ice and meteoric water) at Palmer Station, Antarctica. A shorter sea ice season with early rapid retreat resulted in low phytoplankton biomass with a low proportion of diatoms (2017–2018), while a longer sea ice season with late protracted retreat resulted in the opposite (2018–2019). Despite these differences, phytoplankton seasonal succession was similar in both years: (1) a large‐celled centric diatom bloom during spring sea ice retreat; (2) a peak summer phase comprised of mixotrophic cryptophytes with increases in light and postbloom organic matter; and (3) a late summer phase comprised of small (< 20 μm) diatoms and mixed flagellates with increases in wind‐driven nutrient resuspension. In addition, cell diameter decreased from November to April with increases in meteoric water in both years. The tight coupling between sea ice, meltwater, and phytoplankton species composition suggests that continued warming in the WAP will affect phytoplankton seasonal dynamics, and subsequently seasonal food web dynamics.

Long‐term patterns in ecosystem phenology near Palmer Station, Antarctica, from the perspective of the Adélie penguin

AbstractClimate change is leading to phenological shifts across a wide range of species globally. Polar oceans are hotspots of rapid climate change where sea ice dynamics structure ecosystems and organismal life cycles are attuned to ice seasonality. To anticipate climate change impacts on populations and ecosystem services, it is critical to understand ecosystem phenology to determine species activity patterns, optimal environmental windows for processes like reproduction, and the ramifications of ecological mismatches. Since 1991, the Palmer Antarctica Long‐Term Ecological Research (LTER) program has monitored seasonal dynamics near Palmer Station. Here, we review the species that occupy this region as year‐round residents, seasonal breeders, or periodic visitors. We show that sea ice retreat and increasing photoperiod in the spring trigger a sequence of events from mid‐November to mid‐February, including Adélie penguin clutch initiation, snow melt, calm conditions (low winds and warm air/sea temperature), phytoplankton blooms, shallow mixed layer depths, particulate organic carbon flux, peak humpback whale abundances, nutrient drawdown, and bacterial accumulation. Subsequently, from May to June, snow accumulates, zooplankton indicator species appear, and sea ice advances. The standard deviation in the timing of most events ranged from ~20 to 45 days, which was striking compared with Adélie penguin clutch initiation that varied <1 week. In general, during late sea ice retreat years, events happened later (~5 to >30 days) than mean dates and the variability in timing was low (<20%) compared with early ice retreat years. Statistical models showed the timing of some events were informative predictors (but not sole drivers) of other events. From an Adélie penguin perspective, earlier sea ice retreat and shifts in the timing of suitable conditions or prey characteristics could lead to mismatches, or asynchronies, that ultimately influence chick survival via their mass at fledging. However, more work is needed to understand how phenological shifts affect chick thermoregulatory costs and the abundance, availability, and energy content of key prey species, which support chick growth and survival. While we did not detect many long‐term phenological trends, we expect that when sea ice trends become significant within our LTER time series, phenological trends and negative effects from ecological mismatches will follow.

Assessment of Retinopathy of Prematurity Regression and Reactivation Using an Artificial Intelligence–Based Vascular Severity Score

One of the biggest challenges when using anti-vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment. To evaluate whether an artificial intelligence (AI)-based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment. This prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022. An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images. Analysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20 mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation. Among 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 (P < .001) and 2.9 (1.3) at week 4 (P < .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 (P < .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = -0.9997; P < .001). In this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment.

Provincial Revolution and Regional Anti-Colonialism: The Soviets in Iran, 1920–1921

By focusing on the northern Iranian province of Gilan, this article rethinks the role of non-socialist revolutionary movements in the Soviets’ early retreat from West and South Asia. Drawing primarily on the records of the Russian Foreign Ministry Archive, it probes programmatic divisions within the Soviet Socialist Republic of Iran (SSRI, 1920–1921), a self-governing provincial exclave where the Soviets attempted to reorient social democratic currents toward socialism. This article asks how, in a moment of revolutionary optimism, internal factionalism and the consequent collapse of the SSRI impeded Soviet designs not only in Iran, but also on the colonized and semi-colonized fronts that lay beyond Iranian borders. In so doing, it reflects on the directions of early Soviet engagement with West and South Asian revolutionaries, and the importance of bridging socialist and non-socialist political projects to realizing the broader aim of regional decolonization.

New technologies and machines for stereotactic radiation therapy

AbstractStereotactic radiosurgery and stereotactic body radiation therapy have been increasingly utilized in radiation oncology to treat early stage tumors, metastatic targets, and retreatment of relapsed diseases due to their efficiency, treatment effect, and cost effectiveness over the past two decades. Stereotactic radiosurgery and stereotactic body radiation therapy both demand high specifications for their delivery machines, as they deliver radiation doses with fewer treatment fractions and higher doses per fraction. Manufacturers have either invented specialized technologies solely or customized their existing machines for this purpose. In this paper, we review the major technologies and treatment machines for stereotactic radiosurgery and stereotactic body radiation therapy, describe their main features, and discuss the advantages and disadvantages.

Incremental Healthcare Cost Implications of Retreatment Following Ureteroscopy or Percutaneous Nephrolithotomy for Upper Urinary Tract Stones: A Population-Based Study of Commercially-Insured US Adults.

This study describes the incremental healthcare costs associated with retreatment among adults undergoing ureteroscopy (URS) or percutaneous nephrolithotomy (PCNL) for upper urinary tract stones (UUTS). The IBM® MarketScan® Commercial Database was used to identify adults aged 18-64 years with UUTS treated with URS or PCNL between January 2010 and December 2019. Patients had 12 months of continuous insurance coverage before (baseline) and after (follow-up) the first (index) procedure. The primary outcome was total all-cause healthcare costs measured over the 365-day follow-up period, not inclusive of index costs. Generalized linear models were used to estimate the incremental costs associated with retreatment within 90 (early) or 91-365 days post-index (later) relative no retreatment. The models adjusted for demographics, comorbidities, stone(s) location, treatment setting, procedural characteristics (eg, 1-step vs 2-step PCNL) and index year. Approximately 23% (27,402/119,800) of URS patients were retreated (82% had early retreatments). The adjusted mean total cost was $10,478 (95% CI: $10,281-$10,675) for patients with no retreatment, $25,476 (95% CI: $24,947-$26,004) for early retreatment ($14,998 incremental increase, p<0.01), and $32,868 [95% CI: $31,887-$33,850] for later retreatment ($22,391 incremental increase, p<0.01). Approximately 36% (1957/5516) of PCNL patients were retreated (78% had early retreatments). The adjusted mean total cost was $13,446 (95% CI: $12,659-$14,273) for patients with no retreatment, $37,036 [95% CI: $34,926-$39,145]) for early retreatment ($23,570 incremental increase, p<0.01), and $35,359 (95% CI: $32,234-$38,484) for later retreatment ($21,893 incremental increase, p<0.01). Retreatment during the first year following URS or PCNL was needed in 23% and 36% of patients, respectively, and was associated with an economic burden of up to $23,500 per patient. The high rate of retreatment and associated costs demonstrate there is an unmet need to improve mid- to long-term results in URS and PCNL.

Last Glacial Maximum and early deglaciation in the Stura Valley, southwestern European Alps

We combined data from geomorphologic surveys, glacial modelling, and 10Be exposure ages of boulders on moraines, to investigate the Last Glacial Maximum (LGM) and the early retreat glacial phases in the Stura Valley of the Maritime Alps. We used the exposure ages to reconstruct the timing of standstills or readvances which interrupted the post-LGM withdrawal, initiated ∼24 ka. We mapped and dated the frontal moraines of a first glacial standstill/readvance at a short distance (∼7 km) from the maximum external limit of the LGM, which occurred at ∼22 ka, and a second one at ∼19 ka (Bühl stadial). This morpho-chronologic succession is congruent with that obtained in the adjacent Gesso Valley and, combined with the similarity of Equilibrium Line Altitude values, demonstrates a consistent glacial response in the Maritime Alps to climatic forcing.Our data are chronologically consistent with those of the southern flank of the European Alps, stressing not only a general synchroneity of the LGM across the various sectors, but also that of a LGM recessional standstill or readvance at ∼22 ka. The short distance between the LGM moraines and the recessionary phase moraines, and minimal difference in ELA indicate a modest variation in the mass balance of the Maritime Alps glaciers during this time interval. A similar modest variation between LGM and the first recessional phase glacier mass balance is also found throughout the western sector of the Southern Alps but is considerably more pronounced for the glaciers of the central-eastern sectors. This behaviour can be explained by the interplay between the moisture supplied by southern currents sourced in the Western Mediterranean and that advected by the westerlies sourced in the North Atlantic, which affected the various sectors of the Southern Alps differently.

Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B.

When patients with chronic hepatitis B (CHB) stop nucleos(t)ide analogue (NA) therapy before achieving HBsAg loss, flares often ensue which are challenging to predict early. We determined the incidence, severity, outcome and predictors of flares after NA withdrawal. Forty-five patients enrolled in an RCT were included; 107 patients from an external, prospective cohort were used for validation. Retreatment criteria were pre-defined. Pre- and post-treatment predictors of alanine aminotransferase (ALT) flare (>5× ULN) were evaluated by Cox proportional-hazards regression. Seventy-two weeks after NA withdrawal, 23/45 (51%) patients had developed >5× ULN and 14 (31%) >20× ULN. Median time to develop ALT >5× ULN was 12 weeks after NA withdrawal. Independent predictors of ALT >5× ULN were male sex (HR [95% CI] 3.2 [1.2-8.9]; p=0.03) and serum HBV DNA (1.2 [1.0-1.8]; p=0.03) at Week 6 off-therapy. Specifically, week 6 HBV DNA >10,000 IU/ml predicted ALT >5× ULN (3.4 [1.4-8.4]; p=0.01), which was externally validated. In conclusion, this study on post-treatment flares revealed a high cumulative incidence in CHB. Week 6 HBV DNA >10,000 IU/ml independently predicted flares. The proposed threshold enables prediction of imminent flares in patients who may benefit from closer monitoring and earlier retreatment.

Significance of serum HBV RNA in non-cirrhotic HBeAg-negative chronic hepatitis B patients who discontinue effective antiviral therapy.

HBV RNA is considered as a promising predictor in patients who discontinue nucleos(t)ide analogues (NAs). We determined HBV RNA levels in non-cirrhotic HBeAg-negative patients who discontinued NAs and assessed their predictability for 12-month outcomes. Fifty-seven patients of DARING-B study were included. HBV RNA levels were determined in stored monthly serum samples drawn at 0-3months after end of therapy (EOT). Other markers previously determined in the same cohort including hepatitis B core-related antigen (HBcrAg) were also assessed. HBV RNA at EOT was detectable in 7% of patients, who developed virological/clinical relapse and required retreatment at month 2; in patients with undetectable EOT HBV RNA, 12-month cumulative rates of virological relapse, clinical relapse and retreatment were 68%, 28% and 21%, respectively (p ≤ 0.008). HBV RNA at month-1 after EOT was detectable in 19% of patients being associated with higher probability only of virological relapse (p=0.001). HBV RNA levels correlated significantly to HBV DNA, HBcrAg, ALT and interferon-induced protein-10, but not HBsAg levels. Combined EOT HBV RNA and HBcrAg detection and/or HBsAg >1000 IU/ml was associated only with higher probability of retreatment having higher sensitivity and lower specificity than HBV RNA alone. In conclusion, serum HBV RNA is detectable in a minority of non-cirrhotic HBeAg-negative patients under effective long-term NAs therapy offering low sensitivity but 100% specificity for early retreatment due to severe clinical relapses after NA discontinuation. The combinations of EOT HBV RNA with HBcrAg and/or high HBsAg levels increase sensitivity but decrease specificity for prediction of retreatment after NAs withdrawal.

Causes of death in low-grade B-cell lymphomas in the rituximab era: a prospective cohort study

AbstractLow-grade B-cell lymphomas other than follicular and small lymphocytic lymphoma (LGBCL) account for 10% of all B-cell non-Hodgkin lymphomas. Despite improvements in survival outcomes for these patients, little is known about cause of death (COD) in the rituximab era. For a better understanding, we studied 822 newly diagnosed patients with marginal zone, lymphoplasmacytic, and unclassifiable low-grade B-cell lymphoma prospectively enrolled in the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource from 2002 to 2015. COD was assigned based on medical record review using a standard protocol. At a median follow-up of 107 months, 219 (27%) patients had died. The incidence of lymphoma-related deaths when pooling across subtypes was lower than non–lymphoma-related deaths (10-year incidence, 8.0%; 95% confidence interval [CI]: 6.2-10.4 vs 13.6%; 95% CI: 11.2-16.6). The incidence of lymphoma-related deaths varied by subtype, ranging from 3.7% at 10 years in extranodal marginal zone lymphoma to 19.3% in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Patients with early progression or retreatment events, defined using event-free survival at 24 months from diagnosis, had significantly higher likelihood of lymphoma-related death compared with patients without early events (10-year estimate: 19.1% vs 5.1%, respectively; P < .001), whereas the rates for non–lymphoma-related death were comparable in patients with or without early events (10-year estimates: 11.0% vs 15.3%, respectively). In conclusion, the most common COD in LGBCLs in the first decade after diagnosis was for causes other than lymphoma. Progression or retreatment within the first 2 years of diagnosis was a strong predictor for risk of lymphoma-related death.

Race, rituximab, and relapse in TTP

AbstractImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Robust antiviral responses in severe hepatitis flare persist after early retreatment cessation and lead toward hepatitis B surface antigen loss: A proof‐of‐concept study

Hepatitis B flare has been interpreted as result of immune response against upsurging hepatitis B virus (HBV) and its antigen(s) that may lead to HBV decline/clearance spontaneously. It has been speculated that antiviral therapy could halt the effective immune response with viral persistent as a consequence. A proof-of-concept study was conducted to investigate this issue. Serial biochemical, quantitative hepatitis B surface antigen (HBsAg), interferon-γ (IFN-γ) and tumor-necrosis factor-α (TNF-α) assays were performed in four patients with severe hepatitis flare who had achieved precipitous HBsAg decline within 4weeks of antiviral therapy. TNF-α and IFN-γ were found to be elevated in parallel to upsurging HBV DNA and HBsAg levels in all patients. Higher levels of TNF-α and IFN-γ and levels relative to qHBsAg were observed during and after early termination of therapy within 4weeks in two patients and were followed by further HBsAg decline to <5 IU/ml and even achieved HBsAg loss in one patient. The patient who had stopped therapy on day 44 showed minimal HBsAg decline afterward and the patient who continued therapy showed a 10-fold rebound of qHBsAg from its nadir. The subsequent IFN-γ and TNF-α activity of these two patients was minimal. The results suggest that patients with severe hepatitis flare who achieved precipitous HBsAg decline may have robust immune response to clear the virus, and early termination of antiviral therapy may allow the protective immune response to continue and accelerate HBV decline toward HBsAg loss.

Episodes of Early Pleistocene West Antarctic Ice Sheet Retreat Recorded by Iceberg Alley Sediments.

Ice loss in the Southern Hemisphere has been greatest over the past 30 years in West Antarctica. The high sensitivity of this region to climate change has motivated geologists to examine marine sedimentary records for evidence of past episodes of West Antarctic Ice Sheet (WAIS) instability. Sediments accumulating in the Scotia Sea are useful to examine for this purpose because they receive iceberg‐rafted debris (IBRD) sourced from the Pacific‐ and Atlantic‐facing sectors of West Antarctica. Here we report on the sedimentology and provenance of the oldest of three cm‐scale coarse‐grained layers recovered from this sea at International Ocean Discovery Program Site U1538. These layers are preserved in opal‐rich sediments deposited ∼1.2 Ma during a relatively warm regional climate. Our microCT‐based analysis of the layer's in‐situ fabric confirms its ice‐rafted origin. We further infer that it is the product of an intense but short‐lived episode of IBRD deposition. Based on the petrography of its sand fraction and the Phanerozoic 40Ar/39Ar ages of hornblende and mica it contains, we conclude that the IBRD it contains was likely sourced from the Weddell Sea and/or Amundsen Sea embayment(s) of West Antarctica. We attribute the high concentrations of IBRD in these layers to “dirty” icebergs calved from the WAIS following its retreat inland from its modern grounding line. These layers also sit at the top of a ∼366‐m thick Pliocene and early Pleistocene sequence that is much more dropstone‐rich than its overlying sediments. We speculate this fact may reflect that WAIS mass‐balance was highly dynamic during the ∼41‐kyr (inter)glacial world.

Real-world Early Outcomes and Retreatment Rates Following Water Vapour Ablative Therapy for Symptomatic Benign Prostatic Hyperplasia

BackgroundRezūm water vapour ablation is an effective minimally invasive surgical therapy for the treatment of bladder outflow obstruction. ObjectiveTo present early outcomes and reoperation rates after Rezūm, including an analysis of retreatment rates to gain an insight into optimal patient selection and the durability of the procedure. Design, setting, and participantsData were prospectively collected for consecutive patients undergoing Rezūm for symptomatic benign prostatic hyperplasia between March 2017 and January 2020 at two hospital sites. InterventionRezūm treatment of the prostate. Outcome measurements and statistical analysisPatients were reviewed at 6 wk and 3, 6, and 12 mo after their Rezūm procedure. We evaluated changes in urinary symptoms and the retreatment rate. Results and limitationsA total of 461 patients undergoing Rezūm were analysed. The mean (±standard deviation) follow-up duration was 16.7 ± 10.4 mo. The mean patient age was 67.5 ± 7.8 yr and the mean prostate volume was 56.5 ± 24.0 ml. There was a significant improvement in mean maximum flow rate and postvoid residual volume and in International Prostate Symptom Score and quality-of-life scores (p < 0.0001). During the follow-up period, 21 patients (4.6%) required retreatment, of which 11 cases (2.4%) were within the first year. The retreatments included eight bladder neck incisions or resections, six transurethral resections of the prostate, four Greenlight laser photoselective vaporisations of the prostate, and three Rezūm procedures. The median length of time to a further operation was 11.5 mo (range 3–34). The most common findings at reoperation were an inadequately treated median lobe, an obstructing bladder neck, and in some cases asymmetry of the prostate cavity or recesses within the prostate gland. ConclusionsThis study demonstrates that the beneficial effects of Rezūm observed in the pivotal phase 2 randomised study are transferable to a real-world population with a comparable early retreatment rate. A range of procedures were used for retreatment. The factors dictating which option to select were based on patient concerns regarding side effects, gland volume, symptom profile, and cystoscopy findings. Patient summaryWe investigated outcomes for patients undergoing Rezūm, a water vapour treatment to reduce the size of the prostate in men with obstruction of the bladder outlet because of benign prostate enlargement. This technique yields significant improvements in symptoms and preserves sexual function. The proportion of men needing retreatment was 2.4% in the first year after their Rezūm procedure.