Risk of male breast cancer after Hodgkin lymphoma.

Female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy have a strongly increased risk of breast cancer (BC), but the treatment-specific BC risk in male survivors of HL has not been evaluated. We assessed BC risk in a cohort of 3077 male survivors of 5-year HL treated at age ≤51 years in 20 Dutch hospitals between 1965 and 2013. We estimated standardized incidence ratios (SIRs), absolute excess risks per 10 000 person-years, and cumulative BC incidences. After a 20-year median follow-up, we observed 8 cases of male with BC. Male survivors of HL experienced a 23-fold (95% confidence interval [CI], 10.1-46.0) increased BC risk compared with the general population, representing 1.6 (95% CI, 0.7-3.3) excess BC incidences per 10 000 person-years. The 20- and 40-year cumulative BC incidences after HL treatment were 0.1% (95% CI, 0.02-0.3) and 0.7% (95% CI, 0.3-1.4), respectively. Treatment with chest radiotherapy without alkylating chemotherapy yielded a strongly increased SIR (20.7; 95% CI, 2.5-74.8), which was not significantly different for chest radiotherapy and alkylating chemotherapy (41.1; 95% CI, 13.4-96.0). Males treated with chest radiotherapy and anthracyclines had an SIR of 48.1 (95% CI, 13.1-123.1). Two patients died from BC (median follow-up, 4.7 years). To ensure early diagnosis and treatment, clinicians should be alert to BC symptoms in male survivors of HL.

Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey.

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.

Response to DA-EPOCH-R is associated with activation of 'fitter' cytotoxic T-cells in patients with newly diagnosed double and triple hit high-grade B-cell lymphoma.

Not available.

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

The Investigation of Bone-Implant Connection and New Bone Formation in Fasting and High-Fatty Diet Rats.

BACKGROUND: Hyperlipidemia caused by a high-fat diet (HFD) has many adverse effects on the cardiovascular system, including vascular problems. In addition, a HFD also has significant adverse effects on bone health. AIM: The aim of this study is to examine bone-implant osteointegration and new bone formation in peri-implant defects in fasting and high-fatty diet applied rats. MATERIALS AND METHODS: In this study, 28 female Sprague Dawley rats were used. The rats were divided into four groups, with seven rats in each group: the control group on a normal diet (Group 1) (n = 7), the fasted group (Group 2) (n = 7), the high-fatty diet (HFD) group (Group 3) (n = 7), and the fasted and HFD group (Group 4) (n = 7). Titanium implants with a diameter of 2.5 mm and a length of 4 mm were placed in the right tibia bones of the subjects, and a bone graft corresponding to 2 mm of the implant length was placed in the bone defect applied to the neck region. All rats that continued the administered diet for 12 weeks were sacrificed at the end of the experiment period. The implants and surrounding bone tissue were surgically removed and subjected to biomechanical analysis to assess bone-implant osteointegration and peri-implant new bone formation. RESULTS: It was determined that there was no statistically significant difference between the rats in the control group and the other three groups in terms of bone-implant osteointegration and peri-implant new bone formation (P > 0.05). CONCLUSION: As a result of this study, it was determined that fasting or maintaining a HFD does not adversely affect bone-implant osteointegration or peri-implant new bone formation in the tibias of rats.

Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide: results of a multicenter HOVON phase II trial.

Patients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) as compared to patients without MYC rearrangement. Although intensive chemotherapy regimens yield higher remission rates, toxicity remains a concern. Lenalidomide is an oral immunomodulatory drug which downregulates MYC and its target genes thereby providing support using lenalidomide as additional therapeutic option for MYC+ LBCL. A phase II trial was conducted evaluating the efficacy of lenalidomide (15 mg day 1-14) in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients identified through a nationwide MYC-FISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computer tomography (CT)-scan at end-of-treatment. Secondary endpoints were overall survival (OS), disease-free survival (DFS) and event-free survival (EFS). Eighty-two patients with stage II-IV MYC+ LBCL were treated with 6 cycles of R2CHOP. At EOT, 67% (confidence interval (CI) 58-75%) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates (95% CI) for OS, DFS, EFS were 73% (62-82%), 75% (63-84%) and 63% (52-73%) respectively. In this prospective trial for newly diagnosed MYC+ LBCL patients, we found that administering R2CHOP was safe, and yields comparable CMR and survival rates as in studies applying more intensive chemotherapy regimens. Hence, these findings offer new prospects for MYC+ LBCL patients and warrant comparison in prospective randomized clinical trials. This trial was registered at www.clinicaltrialsregister.eu (#2014-002654-39).

Expression levels of angiogenic growth factors in feline squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the skin in cats. Tumour angiogenesis is the pivotal event for tumour progression and metastasis. We assessed protein and gene expression of angiogenic growth factors including bFGF, VEGF-C, TGF-ß, PDGF-A, PDGF-C and PDGFR-α that possibly contribute to the angiogenic phenotype of feline SCC (FSCC) and could, therefore, be a good target in the treatment of SCC. In the present study, a total of 27 FSCC cases were investigated. Tumour cases were histopathologically classified as well differentiated (10/27), moderately differentiated (5/27), and poorly differentiated (12/27). The expression levels of the growth factors were detected using immunohistochemistry and assessed semi-quantitatively. Growth factor expression levels were evaluated at different locations: in the oral region, in areas exposed to solar UV radiation including the ears, eyelids and nasal planum, and other miscellaneous locations. Our findings have revealed that FSCC arising from different anatomical sites of the body and showing differences in aggressiveness, metastasis, and prognosis may be angiogenesis dependent, and angiogenic key regulators could play a role in the development of FSCC.

Rituximab-PECC induction followed by 90 Y-ibritumomab tiuxetan consolidation in relapsed or refractory DLBCL patients who are ineligible for or have failed ASCT: results from a phase II HOVON study.

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with 90 Y-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade ≥3 adverse events from start of 90 Y-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to 90 Y-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90 Y-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of 90 Y-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and 90 Y-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90 Y-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it.

Extreme Small-Scale Clustering of Droplets in Turbulence Driven by Hydrodynamic Interactions.

We perform three-dimensional particle tracking measurements on droplets in a turbulent airflow. The droplets display the well-known preferential concentration of inertial particles, with an additional extreme clustering at the smallest scales. We explain this additional clustering phenomenon theoretically based on a Stokes-flow description of two spheres including their mutual hydrodynamic interaction and a perturbative small-inertia expansion.

Plerixafor for stem cell mobilization: the current status.

PURPOSE OF REVIEW: Nowadays, plerixafor is approved for patients who fail to mobilize sufficient CD34⁺ cells for an autologous stem cell transplantation. Plerixafor is effective in the majority of these patients, who otherwise could not be treated adequately. We discussed in this review the current status of the optimal use of plerixafor in different clinical diagnoses and settings. RECENT FINDINGS: Plerixafor seems to be more effective in patients with multiple myeloma than in lymphoma. Even patients who had very low circulating CD34⁺ cells before administration of plerixafor have an important benefit. Several strategies in different clinical settings showed an effective response after administration of plerixafor, without the superiority of one strategy. Plerixafor is well tolerated with acceptable toxicity; however, it is an expensive drug. SUMMARY: Plerixafor is an effective drug in patients who fail to mobilize with conventional strategy. No strategy seems superior for the optimal use of plerixafor. More studies focusing on the kinetics and cost-effectiveness are needed.

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor.

BACKGROUND: Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 10(6) /L on 2 consecutive days accompanied by increasing white blood cells. STUDY DESIGN AND METHODS: In this analysis we evaluated retrospectively the outcome of the use of this guideline in the Netherlands. In total 111 patients received plerixafor with a median one administration (range, one to four administrations). Of these patients 55.8% had non-Hodgkin lymphoma, 31.5% multiple myeloma, 8.1% Hodgkin lymphoma, and 4.5% nonhematologic malignancies. RESULTS: In 63.9% patients sufficient numbers of CD34+ cells were collected. In patients with multiple myeloma more successful mobilizations with plerixafor were observed compared to patients with non-Hodgkin lymphoma (71.4% vs. 61.3%). In patients with circulating CD34+ cell counts of at least 2.0 × 10(6) /L before administration of plerixafor a successful mobilization was achieved in 76.5%, and in the patients with very low (0-1 × 10(6) /L) circulating CD34+ cell counts the success rate was 44.2%. CONCLUSION: Application of the HOVON guideline on the just-in-time administration of plerixafor is effective for mobilization of hematopoietic stem cells in the majority of patients. Stem cell yield in patients with non-Hodgkin lymphoma was lower compared to patients with multiple myeloma. Also patients with very low circulating CD34+ cells before addition of plerixafor might benefit from this approach.

Role of first trimester total testosterone in prediction of subsequent gestational diabetes mellitus.

AIM: To assess the role of first trimester maternal testosterone and dehydroepiandrosterone sulfate (DHEA-S) levels in prediction of development of gestational diabetes mellitus (GDM). METHODS: Four hundred and fifty pregnant women were included in this prospective cohort study. All pregnant women with a singleton pregnancy who were not diabetic, had no family history of diabetes, had no history of previous GDM, were of white race and non-smokers were enrolled. Total testosterone and DHEA-S were measured at 11-14 weeks of gestation. The patients were called for routine pregnancy visits and followed accordingly. Forty-two patients did not come to their visits and were excluded. During gestational weeks 24-28, the remaining 408 patients were screened for GDM. The total testosterone and DHEA-S levels were compared between patients with and without GDM. Regression and receiver-operator curve analysis were performed. RESULTS: GDM developed in 22 women (5.7%). Compared with women without GDM, first trimester total testosterone levels were higher among women in whom GDM subsequently developed. The DHEA-S level did not differ. Age, total testosterone and body mass index were found to be independent predictors of GDM development. A total testosterone value of 0.45 ng/mL was found to predict development of GDM with a sensitivity of 63.6% and a specificity of 62.7%. CONCLUSION: First trimester total testosterone has a low testing power for GDM screening with low sensitivity and specificity values and cannot be used as a marker alone. It may have a role in combination with other markers.

The improvement in pelvic floor symptoms with weight loss in obese women does not correlate with the changes in pelvic anatomy.

INTRODUCTION AND HYPOTHESIS: It has been suggested that weight reduction decreases the frequency of urinary incontinence (UI) episodes. However, it is not known if this improvement is associated with anatomical changes in the pelvis. The aim of this study was to investigate the effects of weight loss on UI episodes and pelvic floor anatomy. METHODS: Three hundred seventy-eight overweight/obese women were randomly allocated either to behavioral weight loss or to structured education programs. The patients were evaluated by voiding diary, Pelvic Floor Distress Inventory (PFDI), and Pelvic Organ Prolapse Quantification (POP-Q) system at baseline and after 6 months. RESULTS: The women in the intervention group had a mean weight loss of 9.4 %, whereas the weight in the control group remained almost the same (P < 0.001). While there were no change in stress and urge incontinence episodes in the control group, the mean number of stress incontinence episodes per 3-day diary dropped from 7.96 episodes to 3.11, and the mean number of urge incontinence episodes per 3-day diary dropped from 2.85 episodes to 1.08 in the study group (P < 0.05). Regarding the POP-Q system, only genital hiatus, perineal body, and Ap measurements were significantly lower in the weight loss group than in the control group after 6 months. CONCLUSIONS: Weight reduction provides improvement in episodes of UI, decreases the incidence of drops of urine leakage, and increases quality of life related to pelvic floor symptoms. However, there are little to no changes in the parameters of the POP-Q system with weight reduction.

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma.

PURPOSE: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages. METHODS: We assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses. RESULTS: After a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend = .004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]). CONCLUSION: This study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.