Outcomes of Fedratinib in Routine Treatment of Ruxolitinib-Resistant or -Refractory Patients with Primary and Post-Polycythemia Vera or Essential Thrombocythemia Myelofibrosis: A Nationwide Retrospective Study.

INTRODUCTION: In recent years, fedratinib, a selective JAK2 inhibitor, has emerged as a potential therapeutic option for patients who have failed or are intolerant to ruxolitinib. Despite the promising results observed in clinical studies, real-world evidence from the USA and Europe suggests that the efficacy of fedratinib may be less conclusive. We report the characteristics, treatment patterns, and clinical outcomes of patients with myelofibrosis (MF) treated with fedratinib following ruxolitinib failure in Israel's clinical practice. METHODS: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. RESULTS: We extracted data for 16 eligible patients. Approximately 62.5% of the patients were female, and the median age was 77 (range: 63-85) years. The median duration of ruxolitinib therapy was 17 months (range: 3-84) months. Before the initiation of fedratinib, the median spleen size by palpation was 15.5 cm below the costal margin (range: 4-22 cm). After 3 months the median spleen size was 13 cm below the costal margin (range: 2-21 cm). Only 2 patients showed minimal improvement after 6 months, while 3 patients progressed, and 2 patients showed no change in the spleen size. The spleen response did not improve after 12 months of treatment. At this point, the median spleen size was 19 cm below the costal margin (range: 2-30 cm). Regarding the MF-related symptoms, 43.75% (n = 7) of patients reported some improvement, 37.5% (n = 6) showed no changes, whereas 18.75% (n = 3) of the population complained of worsening. Gastrointestinal toxicity was the most frequent adverse effect of the drug, while 31% of patients died. CONCLUSION: Our observations showed that in MF patients who have failed to ruxolitinib, the therapeutic value from fedratinib may be modest, especially when exposure time to ruxolitinib was more than 12 months. Early switching from ruxolitinib to fedratinib may yield a better result.

Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3-ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission.

OBJECTIVES: Midostaurin, a multikinase and FLT3 inhibitor, is the first non-chemotherapy agent approved and widely adopted for the treatment of FLT3-ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1) needs to be defined. METHODS: This multicenter study retrospectively evaluated the outcome of 119 FLT3-ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo-SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. RESULTS: Ninety-eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo-SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR + CRi rates (P = .002), reduced relapse rates (P = .02), and was remarkably advantageous for high-AR patients (2-year OS 82%). In low-AR patients, the midostaurin effect was much less prominent. CONCLUSIONS: Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high-AR AML patients to whom it should be offered along with allo-SCT in CR1.

Newly diagnosed multiple myeloma patients carrying monoallelic deletion of the whole locus of immunoglobulin heavy chain gene have a better prognosis compared to those with t(4;14) and t(14;16).

The current study evaluated the prognostic significance of the monoallelic deletion of the whole locus of the immunoglobulin heavy-chain (w_del(IGH)) gene compared to translocations t(4;14) and t(14;16) among newly diagnosed multiple myeloma (MM) patients. We retrospectively analyzed clinical (age, gender, and staging) and laboratory data at diagnosis and the overall survival (OS) of 255 newly diagnosed MM patients carrying w_del(IGH) or translocations t(4;14) or t(14;16). Bone marrow samples were examined by morphological and sequential interphase fluorescense in situ hybridization analyses. Among 255 patients, 117 (45.8%) had w_del(IGH), 99 (38.8%) had t(4;14), and 39 (15.3%) had t(14;16). Mean age was 61.6 ± 11.6 years. Groups did not differ significantly in age, gender, or lactate dehydrogenase levels. Patients in the w_del(IGH) group presented more frequently at International Staging System stage I than at stage II/III. Patients in the w_del(IGH) group had significantly fewer additional chromosomal aberrations (1.58) than the other two groups (2.3 and 2.13 in the del(IGH), t(14;16) and t(4;14) groups, respectively, P < 0.0001). Furthermore, the w_del(IGH) group had significantly longer estimated median OS (9.47 years) compared to those with translocations t(14;16) (3.02 years, P = 0.002) or t(4;14) (4.18 years, P = 0.001), respectively. These findings suggest a potential prognostic significance of monoallelic deletion of IGH among these patients. Additional studies are needed to better understand the nature and mechanism of this prognostic factor.

Anchoring the Numeric Pain Scale Changes Pain Intensity Reports in Patients With Chronic But Not With Acute Pain.

BACKGROUND: Despite enormous differences between acute and chronic pain, the numeric pain scale (NRS) is commonly used in pain research and clinical practice for assessing the intensity of both acute and chronic pain. The use of this scale has been challenged as it may fail to accurately reflect the pure intensity of chronic pain. AIM: To compare the effect of anchoring the NRS on the intensity of pain reported by patients with acute vs. chronic pain. METHODS: Patients with acute postoperative or chronic pain (n = 100/group) were requested to rate their: current clinical pain intensity on an NRS from 0 to 100; the intensity of an anchoring pain event on the same scale; and subsequently to rate again their current pain intensity while making reference to the reported intensity of the pain event. The magnitude of correction was compared between the 2 groups. RESULTS: The anchoring pain was rated identically between the groups. However, following anchoring, patients with chronic pain made a significantly larger correction of their pain intensity than did those with acute pain (mean ± standard deviation = 9 ± 9, median [interquartile range] = 10 [0 to 10] vs. 3 ± 7, 0 [0 to 5], respectively; P < 0.0001). More patients in the chronic pain group corrected their pain intensity. Logistic regression showed that chronic pain and female gender significantly increased the likelihood of making the correction (chronic pain: odds ratio 7.2, 95% confidence interval 3.5 to 15.1, P < 0.0001; female gender: odds ratio 2.8, 95% confidence interval 1.4 to 5.5, P < 0.0001). CONCLUSION: The results suggest that anchoring the NRS can potentially improve the accuracy of reported chronic pain intensity.

Unscheduled adolescents return to the emergency department following acute concussion.

OBJECTIVE: Emergency department (ED) visits due to concussion have increased over recent years. We aimed to identify variables associated with unscheduled adolescents return to the ED. METHODS: A retrospective cohort study was conducted. All children aged 11 to 18 years who were admitted to the ED due to concussion between 2011 and 2016 were included. Multivariable logistic regression was performed to identify predictors of ED return. RESULTS: Overall, 616 adolescents were admitted to the ED due to concussion. Within the first week from discharge, 37/616 (6%) patients returned unscheduled to the ED, 21 (3.4%) during the first 48 hours and 16 (2.6%) during the following 3-7 days. Age, gender, ethnicity, diagnosis of concussion on first visit and length-of-stay in the ED were not associated with unscheduled ED returns. Variables that were independently associated with increased odds for an unscheduled ED return included two or more symptoms of concussion [odds ratio (OR): 2.81; 95% confidence interval (CI): (1.16-6.82)], bicycle or motor vehicle accident (OR: 3.48; 95% CI: 1.29-9.4), and performance of CT scan on first visit (OR: 2.47; 95% CI: 1.12-5.48). CONCLUSIONS: The findings suggest that certain variables on the first ED visit can predict an unscheduled return visit in adolescents. ABBREVIATIONS: Emergency department (ED); Length of stay (LOS); computerised tomography (CT).

Pleural Fluid B-Type Natriuretic Peptide Level as an Additional Indicator for the Fluid's Etiology.

BACKGROUND: The identification of the etiology of a pleural effusion can be difficult. Measurement of serum B-type natriuretic peptide (BNP) levels is helpful in the diagnosis of congestive heart failure (CHF) as a cause of respiratory failure, but pleural fluid BNP measurement is still not part of the workup for pleural effusion. OBJECTIVES: To identify the correlation between pleural fluid BNP levels and clinical diagnosis. METHODS: In this cross-sectional study, data from 107 patients admitted to the department of internal medicine between November 2009 and January 2015 were obtained from medical records. Patients underwent a diagnostic thoracocentesis as part of their evaluation. They were grouped according to final diagnosis at discharge and clinical judgment of the attending physician. RESULTS: Serum BNP levels were significantly higher in the CHF patients compared to patients with non-cardiac causes of pleural effusion (1519.2 and 314.1 respectively, P < 0.0001). Mean pleural fluid BNP was also significantly higher in the CHF patients (1063.2 vs. 208.3, P < 0.0001). Optional cutoff points to distinguish between cardiac and non-cardiac etiology of pleural effusion were 273.4 pg/ml (sensitivity 83.3%, specificity 72.3%, accuracy 76.7%) or 400 pg/ml (sensitivity 78.6%, specificity 86.2%, accuracy 83.0%). A strong correlation was found between serum BNP and pleural fluid BNP levels. CONCLUSIONS: High levels of serum BNP in patients presenting with pleural effusion suggest CHF. In cases with doubt regarding the etiology of pleural effusion, high levels of pleural fluid BNP can support the diagnosis, but are not superior to serum BNP levels.

Adult Nephrotic Syndrome after Hematopoietic Stem Cell Transplantation: Renal Pathology is the Best Predictor of Response to Therapy.

Nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (HSCT) is a rare phenomenon usually associated with graft-versus-host disease (GVHD). This systematic review of post-HSCT NS cases reported in the literature aimed to identify risk factors and unique features of the disease in this clinical setting. One hundred sixteen cases of post-HSCT NS published in the English literature between 1988 and 2015 were revealed and analyzed. The median onset of NS was 20.5 months (range, 3 to 174) post-HSCT. NS development was associated with acute or chronic GVHD in 87.2% of cases. Membranous nephropathy (MGN) was the most frequent pathology (65.5%), followed by minimal change disease (MCD) (19%). Complete remission of the NS was achieved in 63.5% of patients (59.1% of MGN cases and 81.3% of MCD cases; P = .15). Patients presenting with MCD recovered at a median of 1.75 months (range, 1 to 12) and with MGN a median of 7 months (range, 1 to 53) (P = .001). NS was treated with corticosteroids alone in 16.8% of patients and with a combination of corticosteroids and other immunosuppressive agents in 73.5% of patients. Univariate analysis failed to identify a single predictive factor of response to therapy. In conclusion, post-HSCT NS usually develops concomitant to GVHD and is associated with high rates of response to therapy. Although most patients were treated with a combination of immunosuppressive drugs, single-agent therapy with steroids may be sufficient in some cases.

Prospective comparison of early bone marrow evaluation on day 5 versus day 14 of the "3 + 7" induction regimen for acute myeloid leukemia.

Evaluation of early response during induction therapy for acute myeloid leukemia (AML) is used for prognostication and re-induction strategy, yet the optimal evaluation time point is unknown. Clearance of bone marrow (BM) blasts by day 14 of therapy does not ensure remission; thus, some patients requiring re-induction are neglected. This study aimed to examine the role of earlier BM evaluation during induction for predicting remission and overall survival. Results of BM testing on the 5th and 14th day of intensive induction were prospectively compared in 127 adult patients with AML. Re-induction was given, based on Day 14 results, to 25 patients. Reduction of the BM blast count to <5% as early as by the fifth day of induction was more specifically associated with the achievement of remission compared to Day 14 (88.2% vs. 60%, respectively). Rapid responders have a better 3-year overall survival (OS). Day 5 results are a stronger predictor of OS by multivariate analysis and better segregate long-term survivors than the Day 14th BM count (66% vs. 30%, P = 0.0001 and 48% vs. 37%, respectively, P = 0.04). The Day 5 evaluation of BM carries significant clinical information. The benefit of prescribing re-induction based on such early evaluation should be prospectively studied.

Sedation with the Combination of Ketamine and Propofol in a Pediatric ED: A Retrospective Case Series Analysis.

BACKGROUND: Literature to date has suggested advantages of sedation with the combination of ketamine and propofol over ketamine alone or propofol alone. However, there is a paucity of data regarding sedation with the combination of ketamine and propofol in pediatric emergency medicine. METHODS: A retrospective case series analysis of children who underwent sedation with the combination of ketamine and propofol in a pediatric emergency department was conducted. Study covariates were extracted from the emergency department medical records. RESULTS: Four hundred twenty-nine patients, 297 males and 132 females, with a median age of 6.8 years (interquartile range, 3.9-10.9 years), underwent sedation by pediatric emergency physicians. Serious adverse events during sedation (SAEDS) were recorded in 52 procedures (12.1%), which included 39 hypoxic events (9.1%), 12 apneic events (2.8%), and 1 laryngospasm (0.2%). All SAEDS were managed successfully, and no child underwent intubation because of an adverse reaction or required hospitalization. Multivariate logistic regression analysis did not reveal any association between age, weight, fasting time, analgesic medication provided before sedation, length of procedure, capnography use, dosages of medications, and the presence of SAEDS. CONCLUSIONS: This is the largest reported series of sedation with the combination of ketamine and propofol in pediatric emergency medicine. Findings suggest that sedation with the combination of ketamine and propofol can be safely performed by a skilled emergency physician.

Bortezomib-cyclophosphamide-dexamethasone (VCD) versus bortezomib-thalidomide-dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis.

Three-drug induction regimens have become the standard of care in newly diagnosed transplant-eligible multiple myeloma patients. Two frequently used protocols are bortezomib, cyclophosphamide and dexamethasone (VCD) and bortezomib, thalidomide and dexamethasone (VTD). Comparisons between the two are lacking. The present study aimed to identify the differences in response rate and toxicity between the two regimens. Databases were searched using the terms 'VTD' or 'VCD' and 'induction regimens for newly diagnosed multiple myeloma'. Prospective trials evaluating initial response in transplant eligible patients were included. The main outcome measures were response rates and adverse events. Eight clinical trials were eligible for analysis. Overall 672 patients were treated with either VCD (n = 157) or VTD (n = 515) as induction therapy. Patients treated with VTD presented with a significantly higher complete/near complete response (34% vs. 6%, P = 0·002) as well as a higher very good partial response rate or better, following induction therapy (62% vs. 27%, P < 0·0001). Although grade 3-4 neurotoxicity was more frequent during VTD therapy (11% vs. 6%, P = 0·057), a higher incidence of overall grade 3-4 adverse events was found in the VCD-treated patients (74% vs. 51%, P < 0·001). VTD induction therapy may be superior in achieving deeper response rate following induction therapy, and is better tolerated.

Strikingly high false positivity of surveillance FDG-PET/CT scanning among patients with diffuse large cell lymphoma in the rituximab era.

Predictive value (PV) of surveillance fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy-rituximab (R) versus chemotherapy only, remains unclear. The aim of the current study was to compare the performance of surveillance PET in DLBCL patients receiving CHOP (cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, and prednisone) alone versus CHOP-R. Institutional database was retrospectively searched for adults with newly diagnosed DLBCL, receiving CHOP or CHOP-R, who achieved complete remission and underwent surveillance PETs. Follow-up (FU) PET was considered positive for recurrence in case of an uptake unrelated to physiological or known benign process. Results were confirmed by biopsy, imaging and clinical FU. One hundred nineteen patients, 35 receiving CHOP and 84 CHOP-R, who underwent 422 FU-PETs, were analyzed. At a median PET-FU of 3.4 years, 31 patients relapsed (17 vs. 14, respectively; P = 0.02). PET detected all relapses, with no false-negative studies. Specificity and positive PV (PPV) were significantly lower for patients receiving CHOP-R vs. CHOP (84% vs. 87%, P = 0.023; 23% vs. 74%, P < 0.0001), reflecting a higher false-positive (FP) rate in subjects receiving CHOP-R (77% vs. 26%, P < 0.001). In the latter group, FP-rate remained persistently high up to 3 years post-therapy. Multivariate analysis confirmed rituximab to be the most significant predictor for FP-PET. In conclusion, routine surveillance FDG-PET is not recommended in DLBCL treated with rituximab; strict criteria identifying patients in whom FU-PET is beneficial are required.

Predicting infections in high-risk patients with myelodysplastic syndrome/acute myeloid leukemia treated with azacitidine: a retrospective multicenter study.

Hypomethylating agents have become the standard therapy for patients with high-risk myelodysplastic syndrome (MDS). In Israel, azacitidine (AZA) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA-treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high-risk MDS and 27 acute myeloid leukemia (AML)], with a median age of 71.6 (range 29-92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin (Hb) and platelet (PLT) counts were found to be associated with infections (24.4% vs. 12.9%, P < 0.0001; 27% vs. 13.5%, P < 0.0001; 20.4% vs. 11%, P < 0.0001 and 29.2% vs. 14.2%, P < 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 109/L and neutrophil count below 0.5 × 109/L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered.

Third BNT162b2 mRNA SARS-CoV-2 Vaccine Dose Significantly Enhances Immunogenicity in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.

COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study longitudinally evaluated humoral and cellular responses to the BNT162b2 vaccine in adult allogeneic HSCT patients. A positive response was defined as antibody titers ≥ 150 AU/mL post-second vaccination. Among 77 included patients, 51 (66.2%) responded to vaccination. Response-associated factors were female gender, recent anti-CD20 therapy, and a longer interval between transplant and vaccination. Response rates reached 83.7% in patients vaccinated >12 months post-transplant. At 6 months post-second vaccination, antibody titers dropped, but were significantly increased with the booster dose. Moreover, 43% (6/14) of non-responders to the second vaccination acquired sufficient antibody titers after booster administration, resulting in an overall response rate of 79.5% for the entire cohort. The BNT162b2 vaccine was effective in allogeneic transplant recipients. Although antibody titers decreased with time, the third vaccination led to their significant elevation, with 93% of third-dose responders maintaining titers above 150 AU/mL at 3 months post-administration.

Immunogenicity and SARS-CoV-2 Infection following the Fourth BNT162b2 Booster Dose among Health Care Workers.

INTRODUCTION: The fourth SARS-CoV-2 vaccine dose was found to protect against infection and more importantly against severe disease and death. It was also shown that the risk of symptomatic or severe disease was related to the antibody levels after vaccination or infection, with lower protection against the BA.4 BA.5 Omicron variants. The aim of our study was to assess the impact of the fourth dose on infection and perception of illness seriousness among healthcare workers (HCWs) at a tertiary health care campus in Haifa, Israel, and to investigate the possible protective effect of antibody levels against infection. METHODS: We conducted a prospective cohort study among fully vaccinated HCWs and retired employees at Rambam Healthcare Campus (RHCC), a tertiary hospital in northern Israel. Participants underwent serial serological tests at 1, 3, 6, 9, 12 and 18 months following the second BNT162b2 vaccine dose. Only a part of the participants chose to receive the fourth vaccine. A multivariable logistic regression was conducted to test the adjusted association between vaccination, and the risk of infection with SARS-CoV-2. Kaplan-Meier SARS-CoV-2 free "survival" analysis was conducted to compare the waning effect of the first and second, third and fourth vaccines. Receiver Operating Characteristic (ROC) curve was plotted for different values of the sixth serology to identify workers at risk for disease. RESULTS: Disease occurrence was more frequent among females, people age 40-50 years old and those with background chronic lung disease. The fourth vaccine was found to have better protection against infection, compared to the third vaccine; however, it also had a faster waning immunity compared to the third vaccine dose. Antibody titer of 955 AU/mL was found as a cutoff protecting from infection. CONCLUSIONS: We found that the fourth vaccine dose had a protective effect, but shorter than the third vaccine dose. Cutoff point of 955 AU/mL was recognized for protection from illness. The decision to vaccinate the population with a booster dose should consider other factors, including the spread of disease at the point, chronic comorbidities and age, especially during shortage of vaccine supply.

Association between IgG antibody levels and adverse events after first and second Bnt162b2 mRNA vaccine doses.

OBJECTIVES: This study sought to correlate the SARS-CoV-2 IgG antibody response level to the BNT162b2 (Pfizer BioNTech) mRNA vaccine after the first and second doses with the reported adverse events. METHODS: This cohort study examined the adverse events profiles of people vaccinated with BNT162b2 in our institute between late 2020 and May 2021. Adverse events, age, and sex were reported using an electronic questionnaire, and their SARS-CoV-2 IgG antibody levels were retrieved from the hospital database. RESULTS: Between 20 December 2020 and 31 May 2021, the adverse events questionnaire was completed by 9700 individuals who received the first vaccine dose and 8321 who received the second dose. After the first and second doses, the average antibody levels were 62.34 AU/mL (mean 4-373) and 188.19 AU/mL (mean 20-392), respectively. All of the adverse events, except local pain, were more common after the second vaccine dose. Multivariate analysis showed that after the first vaccine dose, female sex and younger age (but not IgG titres) were associated with a higher probability of adverse events (OR 2.377, 95% CI, 1.607-3.515, p = 0.000; OR 0.959, 95% CI, 0.944-0.977, p £0.000; OR 1.002, 95% CI, 0.995-1.008, p £0.601; respectively); however, all three parameters were associated with the incidence of adverse events after the second dose (OR 2.332, 95% CI, 1.636-3.322, p = 0.000; OR 0.984, 95% CI, 0.970-0.999, p £0.039; OR 1.004, 95% CI, 1.001-1.007, p £0.022; respectively). DISCUSSION: Adverse events are significantly more common after the second BNT162b2 vaccine dose than after the first dose. We found an association between sex, age, and SARS-CoV-2 IgG antibody titre with the incidence of adverse events.

Re-induction versus salvage for D14-resiudal acute myeloid leukemia: A retrospective multi-center study.

Remission assessment in acute myeloid leukemia has evolved over the recent years with the advent of molecular and flow-based minimal residual disease determination. Nonetheless, early time point such as day 5 and day 14 (D14), still have prognostic and therapeutic implications. D14 refractory disease is regarded as a poor prognostic factor, however the therapeutic intervention is still under debate, with evidence suggesting a successful re-induction might offer similar long-term outcome as D14 aplasia. Others advocate the use of more intensive salvage protocols as a mean to overcome the negative prognostic effect. In the current study, we compare outcome of D14 refractory AML patients treated with either re-induction or salvage protocol. More importantly, we identify response characteristics that might suggest which patients will benefit from re-induction approach. Accurate identification of chemotherapy refractory patients might allow the early incorporation of non-chemotherapy based protocols in the future.

Third BNT162b2 Vaccine Booster Dose against SARS-CoV-2-Induced Antibody Response among Healthcare Workers.

This study assessed humoral response to the third BNT162b2 dose among healthcare workers (HCW). This prospective cohort study of HCW tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) at 1, 3, 6, 9, and 12 months after receiving the second BNT162b2 vaccine dose (tests 1, 2, 3, 4, and 5, respectively). A third (booster) vaccination dose was introduced before test 4. Linear regression model was used to determine the humoral response following vaccine doses. For each serology test, changes in log-transformed antibody concentrations over time, adjusted for age, sex, underlying diseases, steroid treatment, and smoking were described using the general linear mix model. Serology tests were performed at 3, 6, 9, and 12 months after the second vaccine dose in 1113, 1058, 986, and 939 participants, respectively. The third dose was received by 964 participants before the 9-month tests, 797 of whom participated in the 9- and 12-month serology tests. A significant inverse correlation was noted between time from third dose and antibody concentrations (Spearman correlation −0.395; p < 0.001). Age (p < 0.0001; CI 95% −0.005−−0.004), heart disease (p < 0.0001; CI 95% −0.177−−0.052), immunodeficiency (p < 0.0001; CI 95% 0.251−−0.106), and smoking (p < 0.0001; CI 95% −0.122−−0.040) were significantly associated with decreased antibody concentrations. Female sex (p = 0.03; CI 95% 0.013−0.066) was associated with increased antibody concentrations. The third booster dose had a better effect on immunogenicity, with higher antibody concentrations among tested HCW. Heart disease, smoking, and other known risk factors were associated with decreased antibody concentrations.

Volume of fluid consumption during preparation for colonoscopy is possibly the single most important determinant of bowel preparation adequacy.

BACKGROUND: The effectiveness and safety of colonoscopy are directly dependent on the quality of bowel preparation. Multiple risk factors for inadequate bowel preparation (IBP) have been identified; however, IBP is still reported in 20-30% of cases in most studies. We aimed to identify modifiable predictors of the adequacy of bowel preparation using sodium picosulfate, and to recommend easily modifiable parameters to increase the success rate of colonoscopies. METHODS: This was a single-center observational study of adult outpatients referred for an elective colonoscopy. Patients were interviewed prior to colonoscopy; volume of liquids consumed was calculated as number of 200-mL cups showed to the patient. Additional information, including medical history, diagnoses and regular medications, was procured from patients' medical records. Univariate and multivariate regression analyses were performed to identify factors significantly associated with IBP in a subgroup analysis of high-risk patients. RESULTS: The rate of IBP in 1172 subjects was 19.4%. This rate decreased as fluid consumption increased, with a further drop associated with shorter intervals from end of preparation to colonoscopy. Drinking < 1.4 L significantly increased the risk of IBP (odds ratio [OR] 3.62, 95% confidence interval [CI] 2.65-4.95), while drinking ≥2 L was associated with adequate preparation (OR 0.09, 95%CI 0-0.42). These associations were stronger in high-risk individuals. CONCLUSION: Greater fluid intake and short interval to colonoscopy are easily modifiable parameters that can substantially reduce the rate of IBP, especially among high-risk individuals.