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Nevin Manimala Statistics

Clinical Outcomes in Double-Exposed Chronic Lymphocytic Leukemia Patients in Italy

Hematol Oncol. 2026 Mar;44(2):e70184. doi: 10.1002/hon.70184.

ABSTRACT

B-cell receptor inhibitors (BCRi) and B-cell lymphoma-2 inhibitor (BCL2i) improved outcomes of patients with chronic lymphocytic leukemia (CLL), but relapsing after two inhibitors still represent an unmet clinical need. This multicenter real-world study analyzes outcomes of a cohort treated in Italy between May 2017 and September 2023 following prior exposure to both BCRi and BCL2i. The median follow-up after venetoclax initiation was 47 months (IQR 28-56). Of 153 double-exposed patients, 104 (68%) discontinued venetoclax and 53 of them (51%) received a subsequent treatment. Venetoclax was discontinued due to progressive disease (PD) in 51/104 cases (49.0%), with nine deaths occurring rapidly after PD without the administration of any further treatment. Fifty-three patients received treatment after venetoclax: 29/53 (54.7%) received inhibitors (13 cBTKi, 11 idelalisib, 2 BCL2i, 3 non-covalent BTKi), 19/53 (35.8%) received chemoimmunotherapy (CT: 16 intensive, 3 palliative), 5/53 (9.4%) received hematopoietic stem cell transplantation (HSCT). Overall response rate was 50%; median event free survival (EFS) in the groups of inhibitors, CT and HSCT was 11, 2, and 10 months, respectively (p < 0.0001); median overall survival (OS) was 12, 5, and 10 months, respectively (p = 0.020). Disease progression during venetoclax treatment was associated with shorter subsequent EFS compared to discontinuation for other reasons, even if the finding did not reach statistical significance (median EFS 4 vs. 10 months; p = 0.11). No decrease in EFS was associated with del17p and/or TP53 mutations, the use of venetoclax monotherapy or a previous treatment with one versus multiple BCRi. Despite its limitations, this real-world study provides additional insights into double-exposed patients, who still pose a clinical challenge, demonstrating the superior efficacy of inhibitors over alternative treatment options. Enrollment in clinical trial and treatments with novel molecules, if available, may help address this unmet clinical need.

PMID:41778381 | DOI:10.1002/hon.70184

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Demodex parasite density in patients with melasma: a case-control study

Cutan Ocul Toxicol. 2026 Mar 4:1-6. doi: 10.1080/15569527.2026.2639710. Online ahead of print.

ABSTRACT

BACKGROUND: Although multiple factors contribute to the development of melasma, there are reports suggesting a potential role of Demodex parasites in hyperpigmentation. This study aimed to compare the density and prevalence of Demodex infestation between patients with melasma and healthy controls.

METHODS: This case-control study included 35 melasma patients and 35 healthy volunteers. Standard superficial skin biopsies using cyanoacrylate adhesive were taken from the malar regions. Samples were examined via light microscopy, with a density of ≥5 Demodex/cm2 defined as positive.

RESULTS: No statistically significant difference was found between the melasma and control groups in terms of Demodex mite density or positivity rates. Correlation analysis revealed no significant relationship between mMASI scores and Demodex mite density. As a secondary finding, the mean mMASI score was significantly higher in male participants compared to female participants.

CONCLUSION: In this case-control study, we found no statistically significant association between Demodex parasite density and melasma in our study population. While our findings do not support an association in this sample, future large-scale and multicenter studies could further explore the potential role of Demodex in skin disorders that have been suggested by other reports. The single-center design and moderate sample size should be considered when interpreting these results.

PMID:41778367 | DOI:10.1080/15569527.2026.2639710

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Factors influencing time to speech processor upgrades

Cochlear Implants Int. 2026 Mar 4:1-10. doi: 10.1080/14670100.2026.2635191. Online ahead of print.

ABSTRACT

OBJECTIVE: Cochlear implant (CI) speech processors have undergone technological advancements. Therefore, patients upgrade speech processors when new features are available or when their previous device becomes broken and is no longer serviceable. This study aimed to identify factors that impact the time to a speech processor upgrade and to evaluate patient experiences with upgrading and following upgrade.

METHODS: In this retrospective cohort study, 46 CI surgeries at a single tertiary care center in 2017 and that subsequently received a speech processor upgrade were included. Data on patient demographics, hearing loss history, CI manufacturer, insurance type and status, and configuration were collected. Time to first upgrade, reasons for upgrade, patient-reported satisfaction, and speech perception scores were analyzed.

RESULTS: The mean time to a speech processor upgrade was 5.13 years after implantation. The most common reason for an upgrade was the device being over five years old, followed by the device being out of warranty. 45.7% of patients expressed satisfaction with speech processor upgrade, while 8.7% were not satisfied. There were no statistically significant associations between the time to upgrade and demographic factors such as age, sex, insurance type, or CI manufacturer. Following the upgrade, there were no significant changes in speech perception scores.

CONCLUSION: Speech processor upgrades at this center align with when insurance companies typically deem upgrades medically necessary. Demographic factors, insurance, and device manufacturer did not significantly influence time to upgrade. While objective speech perception measures did not significantly improve, many patients reported subjective satisfaction with the upgrade.

PMID:41778354 | DOI:10.1080/14670100.2026.2635191

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Rainfall and Temporal Influences on the Hydrodynamics of a Vertical Subsurface Flow Constructed Wetland Treating Domestic Sewage

Water Environ Res. 2026 Mar;98(3):e70324. doi: 10.1002/wer.70324.

ABSTRACT

This study aimed to evaluate the hydrodynamic behavior of a vertical subsurface flow constructed wetland (VSSF-CW) treating domestic sewage by applying a saline tracer, comparing system performance in operational Years 3 (NR-3) and 5 (NR-5), and assessing the influence of a rainfall event (R-5). Electrical conductivity monitoring was used to construct residence time distribution (RTD) curves for all tests, enabling detailed characterization of hydraulic behavior. As a result, the system exhibited highly dispersed flow (d > 1.21; N < 2.07) with a tendency toward continuous stirred tank reactor (CSTR) behavior. A comparison between NR-3 and NR-5 tests revealed significant differences (p < 0.05, t test) in the hydrodynamic parameters. The rainfall event (R-5) had a statistically significant effect (p < 0.05, t test), decreasing hydraulic retention time, increasing dilution, and enhancing dispersive flow within the treatment unit. These findings highlight the importance of long-term hydrodynamic monitoring in VSSF-CW systems and demonstrate how operational conditions and external factors such as rainfall can influence treatment performance.

PMID:41778349 | DOI:10.1002/wer.70324

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Is Two Better Than One? Pelvic Fixation Strategies in Neuromuscular and Early-onset Scoliosis: A Comparative Analysis of S1S2-iliac and S2-iliac Screws

J Pediatr Orthop. 2026 Mar 4. doi: 10.1097/BPO.0000000000003257. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with neuromuscular (NM) and early-onset scoliosis (EOS), spinal instrumentation and fusion treatments present significant challenges, particularly in achieving stable pelvic fixation and correcting pelvic obliquity (PO). This study aimed to evaluate whether dual sacroiliac (S1-iliac and S2-iliac) screw constructs improve PO correction and reduce complications compared with S2-iliac screws alone in patients with NM and EOS.

METHODS: A retrospective review of 77 patients with NM or EOS requiring pelvic fixation was conducted. Patients were divided into 2 groups: (1) bilateral S1-iliac and S2-iliac screws (S1-S2 group, n=22) and (2) bilateral S2-iliac screws alone (S2 group, n=55). Preoperative and postoperative major curves and PO were assessed, along with complication rates, including implant prominence, screw pullout, breakage, infection, and revision surgery.

RESULTS: Both groups achieved similar main curve corrections at final follow-up (S2=53%, S1-S2=64%, P=0.121). The mean preoperative major curve for the S2 and S1-S2 groups was 63.7 degrees (range 20 to 106 degrees) and 68.9 degrees (range 39 to 135 degrees), respectively. At final follow-up, the mean curve measured 29.4 degrees (range 3 to 82 degrees) and 23.4 degrees (range 7 to 48 degrees), corresponding to 54% and 66% correction, respectively. Preoperative PO averaged to 11.1 degrees (range 0 to 36 degrees) and 17.5 degrees (range 2 to 36 degrees) in S2 and S1-S2 groups, respectively. At final follow-up, PO measured 4.5 degrees (range -3 to 23 degrees) and 6.3 degrees (range 0 to 15 degrees), respectively. In all, 18% (4/22) of patients in the S1S2 group and 23% (13/55) of patients in the S2 group showed complications. Implant breakage occurred in 1 patient in the S1S2 group and 7 in the S2 group (P=0.427). Revision surgery was required in 5 patients in the S2 group and 1 in the S1S2 group (P=0.668).

CONCLUSIONS: Bilateral S1S2-iliac screws were successfully placed and provided early improvements in PO correction compared with S2-iliac screws alone. However, differences in PO correction and complication rates were statistically insignificant at final follow-up. Further prospective studies with larger cohorts and longer follow-up are needed to assess potential long-term biomechanical advantages of dual fixation.

LEVEL OF EVIDENCE: Level III.

PMID:41778304 | DOI:10.1097/BPO.0000000000003257

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Genotype-Phenotype Correlation of Hereditary Plasminogen Deficiency: Molecular Mechanisms From 18 Patients With Cerebral Infarction

Haemophilia. 2026 Mar 4. doi: 10.1111/hae.70248. Online ahead of print.

ABSTRACT

INTRODUCTION: Hereditary plasminogen (PLG) deficiency is a rare congenital fibrinolytic disorder and a rare disease. This study conducted gene sequencing and statistical analysis on patients with cerebral infarction (CI) and decreased PLG activity (PLG:A) to explore the relationship between PLG gene variants and hereditary thrombotic diseases.

AIM: To analyse PLG gene variants in 18 patients with hereditary PLG deficiency and to investigate the associated clinical manifestations.

METHODS: This Retrospective Study Included 18 Patients With CI and Decreased PLG:A Who Were Admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2021 to May 2025. The patients Ranged in Age from 16 to 70 years. Peripheral blood Samples Were Collected Before Treatment to Determine Relevant Coagulation Indicators Such As PLG:A, PLG antigen (PLG:Ag), protein C activity. Polymerase chain reaction (PCR) followed by direct sequencing was performed to analyse whole genome sequence of the PLG gene. Suspected variants were confirmed by reverse sequencing.

RESULTS: The 18 patients’ cranial magnetic resonance (MRI) revealed recent cerebral infarct lesions in all cases. PLG:A levels ranged from 19% to 67%. All patients were diagnosed with dysplasminogenemia. Genetic analysis identified four types of PLG gene variants: c.1858G > A (p.Ala620Thr), c.398A > G(p.His133Arg), c.2108G > A(p.Gly703Asp), and c.1702G > A (p.Gly568Arg). The p.Ala620Thr mutation was the most frequent, while p.His133Arg and p.Gly568Arg were newly identified variants.

CONCLUSION: Patients with hereditary PLG deficiency resulting from PLG gene variants are at a significantly increased risk of CI, potentially attributable to diminished PLG catalytic activity and consequent impairment of fibrinolytic function.

PMID:41778291 | DOI:10.1111/hae.70248

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Haematology and biochemistry reference intervals of Galapagos short-eared owls (Asio flammeus galapagoensis) from Floreana Island

Conserv Physiol. 2026 Mar 2;14(1):coag013. doi: 10.1093/conphys/coag013. eCollection 2026.

ABSTRACT

To limit the impact of invasive predator species on the ecosystem of Floreana Island, Galapagos, a large-scale rodent eradication program was implemented. Due to the significant risk of secondary exposure to rodenticide, a mitigation tactic was used to protect the only native raptor found on Floreana, the Galapagos short-eared owl (Asio flammeus galapagoensis). A large proportion of the owl population was brought into human care in July 2023 with the goal to release back to the wild following the completion of the eradication program and reduction of the risk of exposure to rodenticides. During this time under human care, health examinations including blood collection for assessment of haematology and biochemistry parameters were completed. Descriptions of leukocyte morphology and population-based reference intervals (RI) are reported here utilizing results from 62 clinically healthy adults. Sex was determined using polymerase chain reaction, allowing for comparisons between males (n = 29) and females (n = 33). Statistically significant differences were found for several parameters: packed cell volume, relative and absolute monocyte counts, total protein, calcium and phosphorus levels were higher in females, while uric acid and glucose levels were significantly higher in males. These baseline RI are an important tool for assessment of this unique population while under human care, and will allow for comparisons and continued health monitoring after release back to the island of Floreana.

PMID:41778266 | PMC:PMC12952920 | DOI:10.1093/conphys/coag013

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The Pulmonary Hypertension Global Patient Survey: Groups 2 and 3

Pulm Circ. 2026 Mar 2;16(1):e70256. doi: 10.1002/pul2.70256. eCollection 2026 Jan.

ABSTRACT

In this first global study of patient perspectives in Group 2 and 3 PH, we demonstrate that those with Group 3 PH report significantly greater adverse impacts on physical and mental wellbeing than those in Group 2 or Group 1, despite a lower treatment side-effect profile.

PMID:41778265 | PMC:PMC12951357 | DOI:10.1002/pul2.70256

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The Pulmonary Hypertension Global Patient Survey: Understanding the Invisible Burden of Paediatric Pulmonary Hypertension

Pulm Circ. 2026 Mar 2;16(1):e70269. doi: 10.1002/pul2.70269. eCollection 2026 Jan.

ABSTRACT

The Pulmonary Hypertension Global Patient Survey (PH GPS) provides the first international examination of experiences among children with pulmonary hypertension (PH) and their caregivers. Through an online survey distributed via PH associations across 32 countries, we collected responses from 136 caregivers about diagnostic journeys, treatment experiences, healthcare access and research participation. Qualitative analysis revealed challenges around the ‘invisible’ nature of PH, with caregivers describing how schools and communities sometimes doubted their child’s limitations in the absence of visible symptoms, adding to family burden. Quantitative findings demonstrated extensive caregiver burden with 40% providing constant care while facing significant employment consequences, including leaving work altogether, reduced hours, or career changes. Although 78.8% of children accessed specialist centres, significant barriers persisted: 41.2% encountered diagnostic delays exceeding 6 months, 34.8% travelled over 2 h for appointments and 27.7% received no healthcare cost reimbursement. Treatment experiences revealed 37.7% of children experienced side effects, yet only one-third discussed changes with their clinical teams, reflecting pragmatic decisions within limited therapeutic options. Research participation was low (19.2%), though families with trial experience showed greater willingness for future participation, compared to those without experience (70.8% vs. 49.5%). Barriers centred on awareness gaps (16.4%), safety concerns (14.5%), and age-related considerations (10.9%), distinct from adult PH populations where logistical challenges predominate. These findings demonstrate that paediatric care must extend beyond medical management to address family needs including social-work assistance for benefits navigation, flexible care delivery models incorporating telemedicine, pro-active communication about treatment tolerability and research protocols designed with families from inception.

PMID:41778264 | PMC:PMC12951355 | DOI:10.1002/pul2.70269

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The Pulmonary Hypertension Global Patient Survey: Physical and Psychosocial Impacts on Health-Related Quality of Life

Pulm Circ. 2026 Mar 2;16(1):e70264. doi: 10.1002/pul2.70264. eCollection 2026 Jan.

ABSTRACT

The Pulmonary Hypertension (PH) Global Patient Survey provides the first truly international description of the symptomatic burden of PH and its treatment on patient’s health-related quality of life (HRQoL). From 3329 adult responses across 88 countries, the “invisible” nature of PH is an over-arching theme, with repercussions on socialisation, relationships and employment. Emotional burden is common with 35.6% feeling misunderstood, 33.4% angry or frustrated and 32.0% isolated. A reduced capacity for paid employment, in combination with healthcare/medication costs and difficulty in accessing social and financial support, compound societal exclusion and isolation. Physical limitations are almost universally reported (78.6%) with poor sleep quality (42.3%) the greatest factor in physical well-being. Treatment side-effects are common (46.7%), are greatest with parenteral therapies, but improve with age. Women of child-bearing age bear the brunt of PH physical and psychological burden, compounded by inconsistent messages from specialist services surrounding pregnancy and contraception. Patient-reported outcome measures (PROM) accurately reflect impacts from PH but are underutilised in clinical practice. Many respondents would like to be better able to discuss their emotional symptoms with their PH specialist (but often find a lack of empathy). Psychological support is a highly requested, but frequently unmet, need reinforcing the importance of holistic care models and multiagency working in managing patients with PH.

PMID:41778263 | PMC:PMC12951358 | DOI:10.1002/pul2.70264