Supplement of Vitamin D for early-stage Chronic Lymphocytic Leukemia Patients is Associated with a Longer Time to first Treatment.

Low levels of vitamin D are associated with a shorter time to first treatment (TTFT) and inferior overall survival in patients with Chronic Lymphocytic leukemia. But whether vitamin D supplement affects the clinical course of CLL patients, remains an open question. In the current study, we aimed to retrospectively explore the clinical benefit of Vitamin D supplement, or one of its analogues, on TTFT and treatment-free survival (TFS) in a large cohort of patients with asymptomatic CLL, who were under watch and wait approach. Among the 3,474 patients included in the study, 931 patients (26.8%) received either vitamin D supplement or its analogue, for a minimum of 6 months. We found that vitamin D supplement was statistically significant for longer TTFT in the young cohort (age<=65) and was associated with a longer TFS for all ages (p-value=0.004). Among non-vitamin D users, the median TFS was found to be 84 months, while among vitamin D supplement users the median TFS extended to 169 months. In conclusion, our long-term retrospective study demonstrates that the administration of vitamin D to patients with CLL in a watch and wait active surveillance is significantly associated with a longer treatment free survival (in any age) and a longer time to first treatment among young patients (age<=65). A prospective clinical trial is needed to validate results.

Improved Survival of Patients With Chronic Lymphocytic Leukemia Between 1998-2022, Including the Era of Target Therapies With BCL2 and BTK Inhibitors.

BACKGROUND/AIM: The treatment for chronic lymphocytic leukemia (CLL) has changed dramatically over the last two decades. The current study aimed to investigate the impact on overall survival (OS) and time to next treatment (TTT) among CLL patients from 1998 to 2022. PATIENTS AND METHODS: The cohort was based on data obtained from electronic medical records of Maccabi, the second largest healthcare organization in Israel. All included patients were diagnosed with CLL based on the IWCLL criteria and complete clinical, laboratory, and treatment data were available. The study encompassed 3,964 patients diagnosed with CLL during the specified study period. RESULTS: Patients with CLL who required therapy were divided into three eras based on the dominant treatment approach: chemotherapy alone before 2010, therapy with chemotherapy and anti-CD20 between 2010 and 2017, and therapy with targeted agents between 2017 and 2022. Median OS was 4.1 years, 7.5 years, and not reached, respectively. The six-year OS rates were 40%, 55%, and 69%, respectively, (p=0.0001). The median time to the next treatment improved from 5.5 years before 2010, to 8.3 between 2010-2017, to not reached after 2017 (p=0.0021). CONCLUSION: Marked improvements in survival subsequent to fundamental changes in first-line therapy were found in patients with CLL from before 2010 to after 2017.

The course of patients with hairy cell leukemia during the omicron surge of the Covid-19 pandemic.

In this study, we aim to explore the outcomes of Covid-19 infection in patients with Hairy cell leukemia (HCL). The cohort is based on data obtained from electronic medical records. It includes 218 consecutive patients diagnosed with HCL between 16 June 1998, and 20 September 2022, out of which the coronavirus has infected 85 patients during the Omicron surge. Out of 85 patients with HCL who were infected by Covid-19; 7 patients (8.2%) have been hospitalized, and the mortality rate was 2.3% (two patients). Thirteen of the 85 patients had been infected by Covid-19 in previous waves, including 9/13 after vaccination, and none of them developed a severe disease. Humoral immune response after three doses of the BNT162b2 mRNA vaccination regimen was evaluated in 40 patients and was attained in 67.5%. Based on multivariate analysis: unfavorable outcome was significantly more common in patients with HCL above 65 years old, who had at least one cytopenia, and with comorbidity of cardiovascular disease or asplenia. Our results indicates that the course of COVID-19 in patients with HCL during the Omicron wave has been improved relatively favorable.

Clinical Outcomes of COVID-19 in Mycosis Fungoides and Sezary Syndrome.

INTRODUCTION: Haemato-oncologic patients are more susceptible to severe infections with SARS-CoV-2. We aimed to assess the clinical outcomes of SARS-CoV-2 infection among patients with Mycosis Fungoides and Sezary Syndrome (MF/SS). METHODS: The data were retrieved from anonymized electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. Patients diagnosed with MF/SS were included in the study. COVID-19 PCR test results together with sociodemographic and clinical data were extracted and analyzed to evaluate the association of COVID-19 with clinical outcomes. RESULTS: In the period of 2020-2022, 1,472 MF/SS patients were included in the study. Among them, 768 (52%) had SARS-CoV-2 infection. The hospitalization rate was 2.9% and infection by the Delta variant was associated with the highest hospitalization rate (7.7%). The hospitalization rate was lower among fully vaccinated patients (p = 0.032) but higher for patients older than 65 (p < 0.001) and patients with SS (vs. MF) (p < 0.001) or COPD (p = 0.024) diagnosis. There was a tendency for decreased hospitalization among patients treated with nirmatrelvir + ritonavir within 5 days of infection, with a 79% risk reduction, although it was not statistically significant (p = 0.164). CONCLUSION: Patients with MF/SS do not necessarily have worse COVID-19 outcomes compared to the general population.

Pregnancy Course of 10 Women Diagnosed with Chronic Lymphocytic Leukemia.

Pregnancies following diagnosis of chronic lymphocytic leukemia (CLL) are rare events, mainly because the disease is typically diagnosed in the elderly. Literature on the topic is based only on case reports, and limited data are available on the influence of pregnancy on CLL course. In this retrospective study, we aimed to summarize the clinical and laboratory course of 10 women with CLL who became pregnant. None of the patients had significant changes in blood count during or after pregnancy or had complications such as infection, autoimmune phenomenon, or preeclampsia. Four out of 10 pregnancies were terminated with an early miscarriage. Following labor, 1 patient started anti-CLL treatment due to preexisting anemia, but none of the women required therapy during CLL progression during the first 2 years of follow-up. We conclude that based on our serial, pregnancy does not negatively impact on CLL course.

The Effectiveness of Bivalent mRNA Omicron Containing Booster Vaccines Among Patients With Hematological Neoplasms.

BACKGROUND/AIM: Last year was characterized by the appearance of novel SARS-CoV-2 virus variants, mainly the omicron sub-lineages BA.2.12.1, BA.4, and BA.5, which have confirmed resistance to the acquired immune response developed following first-generation mRNA vaccines. Given the ability to use mRNA technology to respond quickly to variant strains, novel bivalent vaccines against novel omicron variants were generated. In the current work, we evaluated the efficacy and safety of novel bivalent mRNA Omicron-containing booster vaccines among patients with hematological neoplasms, including both lymphoproliferative and myeloid malignancies. PATIENTS AND METHODS: Cohort patients were obtained from electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. We analyzed the outcome of all patients with hematological neoplasms, between September 21, 2022, and December 31, 2022, who were identified as having SARS-CoV-2 infection based on polymerase chain reaction (PCR) tests. The Kaplan-Meier method was used to compare the proportion of patients hospitalized for SARS-CoV-2 infection within 30 days among recipients and non-recipients of omicron vaccine. RESULTS: During the study period, 472 patients were infected with Omicron. We compared the outcome of 70 patients who received the bivalent mRNA booster to 402 who did not. Fewer bivalent recipients needed COVID-19-related hospitalization [2 of 70 (2.9%)] in comparison to the non-vaccinated cohort [42 of 402 (10.4%)] (p-value=0.0304). This represents an 89% relative risk reduction in COVID-19-related hospitalization in patients with hematological neoplasms. The median duration of hospitalization was 7 days for the non-vaccinated group and 4 for the vaccinated group. A statistically significant increase in ischemic stroke rates due to bivalent mRNA Omicron-containing booster vaccine was not observed. CONCLUSION: The bivalent Omicron-containing vaccine mRNA booster has a protective effect in preventing and shortening hospitalization in patients with hematological neoplasms with an acceptable safety profile.

Sarcopenia as Manifested by L3SMI Is Associated with Increased Long-Term Mortality amongst Internal Medicine Patients-A Prospective Cohort Study.

Background: Sarcopenia and Frailty are syndromes that affect the clinical outcomes of patients suffering from a wide range of diseases. The use of Computed Tomography (CT) is well established for Sarcopenia evaluation via estimation of the Skeletal Muscle Index (SMI) at the level of the third lumbar vertebra (L3SMI). Nevertheless, the association of more readily available biomarkers of Sarcopenia and clinical outcomes is desired. Recent studies have associated low Alanine amino-transferase ALT (SGPT) levels with Sarcopenia and frailty. The current study aimed to establish the association between low L3SMI and the aforementioned indices of Sarcopenia, frailty and poor clinical outcomes. Methods: A cohort study of patients admitted to the internal medicine department at a tertiary medical center. Sarcopenia was determined as L3SMI, lower than 53 cm2/m2 in men and 41 cm2/m2 in women. Clinical and mortality data was collected from the medical record. Results: Of the 187 patients recruited (mean age 70.4 ± 9.2, 59% males), 116 (62%) had Sarcopenia, based on L3SMI values. Sarcopenic patients were older, predominantly male, had lower BMI, lower mid-arm muscle circumference (MAMC) and low ALT values upon admission. L3SMI values significantly correlated with age and MAMC among males (R = −0.38, p < 0.001, R = 0.35, p < 0.001, respectively). Sarcopenia was associated with higher, one-year mortality (HR = 2.60, 95% CI 1.06−6.37, p = 0.036) and shorter all-time survival (HR = 2.91, 95% CI 1.35−6.29, p = 0.007). The association with all-time survival remained after adjusting for age and sex (HR = 2.38, 95% CI 1.07−5.29, p = 0.034). Conclusion: As defined by low L3SMI value, Sarcopenia is a poor prognostic factor for the general internal ward patient population. As part of personalized medicine, physicians may benefit from measuring L3SMI value, as indicated by commonly performed CT scans, to objectively assess their patient's risk of suffering from Sarcopenia and frailty-associated complications.

Mpox Infection in a Developed Country: A Case Report.

This is the first Israeli case report of mpox (monkeypox) disease, as it is manifested in the current outbreak. This manuscript depicts two detailed patient journeys of Israeli men in their 30s who were diagnosed in recent months, depicting their symptoms, presumed exposure, and outcomes. The two cases were atypical compared to the clinical presentation prior to the current outbreak but were similar to other recent reported cases; they differed in their prodromal presentation. Importantly, both patients described that significant anxiety around the diagnosis dominated their journey while sharing that a concern is rising in the GBMSM community, a concern that should be addressed by healthcare providers.

Fluoride ion release and solubility of fluoride enriched interim cements.

STATEMENT OF PROBLEM: Interim and definitive restorations cemented with interim cements for a prolonged interval are susceptible to bacterial infiltration and caries formation. PURPOSE: The purpose of this in vitro study was to evaluate the long-term fluoride release and solubility of aged ZnO-based interim cements enriched separately with 0.4% NaF and SnF2. MATERIAL AND METHODS: Four different brands of cements (Tempbond, Tempbond NE, Procem, and Freegenol) were tested for fluoride release and solubility. For every test, 6 disk specimens of each cement with NaF and SnF2, and 6 with no fluoride enrichment (control) were fabricated, for a total of 72 specimens. The disks were incubated in deionized water. Fluoride ion release was recorded at 1, 7, 14, 21, 63, 91, and 182 days. Solubility was calculated as weight percent after 90 days of incubation. The data were analyzed by analysis of variance with repeated measures and the Tukey honestly significant difference post hoc test (P<.05). RESULTS: Cements mixed with fluorides released fluoride ions for at least 182 days. Cements mixed with NaF released more fluoride ions than those mixed with SnF2 (P<.001). The cumulative release rates from all the tested cements mixed with either NaF or SnF2 were linear with respect to t(½) (r>.97), indicating a diffusion-controlled fluoride release. Cement and fluoride types were the main affecting factors in fluoride ion release. The addition of fluorides slightly increased the solubility of the cements. CONCLUSIONS: Given their long-term sustained and diffusive controlled release, these fluorides, particularly NaF when mixed with ZnO-based interim cements, may be useful for caries prevention under provisionally cemented restorations.