Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial.

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.

Long-term follow-up of VIALE-A: Venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia.

Venetoclax-azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE-A study (NCT02993523). Here, long-term follow-up is presented to address survival benefit and long-term outcomes with venetoclax-azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax-azacitidine or placebo-azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE-A, 431 patients were enrolled to venetoclax-azacitidine (n = 286) or placebo-azacitidine (n = 145). At 43.2 months median follow-up, median OS was 14.7 months (95% confidence interval [CI], 12.1-18.7) with venetoclax-azacitidine, and 9.6 months (95% CI, 7.4-12.7) with placebo-azacitidine (hazard ratio, 0.58 [95% CI, 0.47-0.72], p < .001); the estimated 24-month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any-grade hematologic and gastrointestinal adverse events were most common in venetoclax-azacitidine and placebo-azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long-term efficacy and safety confirm venetoclax-azacitidine is an improvement in standard-of-care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities.

Evaluation of interleukin-8 levels in the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies.

This study aimed to determine the level of interleukin (IL)-8 in diagnosing of invasive pulmonary aspergillosis (IPA). We conducted this study with 50 controls and 25 IPA patients with haematological malignancies. Demographic data, haematological diagnoses, chemotherapy regimen, galactomannan level, fungal culture, and computed tomography findings of the patients were evaluated prospectively. IL-8 levels were studied with the ELISA method. The mean age of patients in the case group was 60.84 ± 15.38 years, while that of the controls was 58.38 ± 16.64 years. Of the patients, 2/25 were classified as having 'proven', 13/25 as 'probable', and 10/25 as 'possible' invasive aspergillosis (IA). Serum IL-8 levels were found to be significantly higher in the case group compared to the controls. There was a negative correlation between serum IL-8 levels and neutrophil counts and a positive correlation with the duration of neutropenia. A significant cutoff value for serum IL-8 parameter in detecting IPA disease was obtained as ≥274 ng/l; sensitivity was 72%; specificity was 64%; PPV was 50%; and NPV was 82%. In the subgroup analysis, there was no significant difference in serum IL-8 levels between the case group and the patients in the neutropenic control group, while a significant difference was found in with the patients in the non-neutropenic control group. Serum IL-8 levels in neutropenic patients who develop IPA are not adequate in terms of both the diagnosis of the disease and predicting mortality. New, easily applicable methods with high sensitivity and specificity in diagnosing IPA are still needed.

Although a significant cutoff value for serum interleukin (IL)-8 was found in the diagnosis of IPA, there was no statistical difference in serum IL-8 when subgroup analysis was performed with neutropenic control patients. Therefore, serum IL-8 is not a successful marker in diagnosing neutropenic patients with IPA.

A comparison of the effects of thoracolumbar interfascial plane (TLIP) block and erector spinae plane (ESP) block in postoperative acute pain in spinal surgery.

PURPOSE: Spinal surgeries are a very painful procedure. New regional techniques for postoperative pain management are being considered. The present study aimed to evaluate the hypothesis that the ultrasound-guided erector spinae plane (ESP) block would lead to lower opioid consumption compared to the thoracolumbar interfascial plane (TLIP) block after lumbar disk surgery. The study's primary objective was to compare postoperative total opioid consumption, and the secondary objective was to assess postoperative pain scores. METHODS: Sixty-eight patients who underwent elective lumbar disk surgery were randomly assigned to either the ESP block group or the TLIP block group. The current pain status of the patients in both the ESP and TLIP block groups was assessed using the Numerical Rating Scale (NRS) at specific time intervals (30 min, 1, 6, 12 and 24 h) during the postoperative period. The number of times patients administered a bolus dose of patient-controlled analgesia, (PCA) within the first 24 h was recorded. RESULTS: In the ESP group, the total opioid consumption in terms of morphine equivalents was found to be significantly lower (ESP group: 7.7 ± 7.0; TLIP group: 13.0 ± 10.1; p < 0.05). The NRS scores were similar between the groups at 30 min, 1, 6, and 12 h, but at 24 h, they were significantly lower in the ESP group. Moreover, the groups had no significant difference regarding observed side effects. CONCLUSION: This study demonstrated the analgesic efficacy of both techniques, revealing that the ESP block provides more effective analgesia in patients undergoing lumbar disk surgery.

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia.

BACKGROUND: Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study. METHODS: We randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo. All patients received a standard dose of azacitidine (75 mg per square meter of body-surface area subcutaneously or intravenously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily, in 28-day cycles. The primary end point was overall survival. RESULTS: The intention-to-treat population included 431 patients (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo [control] group). The median age was 76 years in both groups (range, 49 to 91). At a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine-venetoclax group and 9.6 months in the control group (hazard ratio for death, 0.66; 95% confidence interval, 0.52 to 0.85; P<0.001). The incidence of complete remission was higher with azacitidine-venetoclax than with the control regimen (36.7% vs. 17.9%; P<0.001), as was the composite complete remission (complete remission or complete remission with incomplete hematologic recovery) (66.4% vs. 28.3%; P<0.001). Key adverse events included nausea of any grade (in 44% of the patients in the azacitidine-venetoclax group and 35% of those in the control group) and grade 3 or higher thrombocytopenia (in 45% and 38%, respectively), neutropenia (in 42% and 28%), and febrile neutropenia (in 42% and 19%). Infections of any grade occurred in 85% of the patients in the azacitidine-venetoclax group and 67% of those in the control group, and serious adverse events occurred in 83% and 73%, respectively. CONCLUSIONS: In previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone. The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group. (Funded by AbbVie and Genentech; VIALE-A ClinicalTrials.gov number, NCT02993523.).

Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.

BACKGROUND: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. RESULTS: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. CONCLUSIONS: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment. (Supported by Celgene; QUAZAR AML-001 ClinicalTrials.gov number, NCT01757535.).

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data.

Glofitamab is a CD3xCD20 bi-specific antibody with two fragments directed to the CD20 antigen and a single CD3-binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B-cell lymphoma. However, the real-world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B-cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty-three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first-line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow-up time was 5.7 months. In efficacy-evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression-free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment-responsive patients progressed during the study period, and their estimated 1-year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab-related febrile neutropenia. This is the largest real-world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.

Subdural Hematomas in Adults and Children.

Subdural hematoma is a common entity encountered by the neurosurgeon. The disease has acute, subacute, and chronic forms. Management of the disease changes according to the etiology of the lesion, yet the main goals are, as with most neurosurgical interventions, decompression of neural tissue and restoration of perfusion. Due to various forms and causes of the disease such as trauma, anticoagulant/antiaggregant use, arterial rupture, oncologic hemorrhages, intracranial hypotension, and idiopathic hemorrhages, several approaches for management have been documented in the literature. Herewith, we present various up-to-date management options for the disease.

Ultrasonographic Measurement of Median Nerve Cross-Sectional Area in Evaluating Carpal Tunnel Release Outcomes.

PURPOSE: Earlier research has explored carpal tunnel release (CTR) surgery outcomes using electrodiagnostic tests (EDX). However, evaluation of the median nerve before and after CTR by ultrasound (US) is understudied. This study aimed to establish the outcomes of CTR by EDX and US, and examine the correlation between the clinical improvement and US after CTR. METHODS: The sample consisted of 172 wrists that underwent CTR. Pain was assessed using the visual analog scale (VAS). The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), including the symptom severity and function subscales, was applied before and 3 months after CTR. The proximal and distal cross-sectional areas (CSAs) of the median nerve were measured using US, and EDX was performed before and 3 months after CTR. RESULTS: Patients had mean preoperative and postoperative VAS scores of 7.7 ± 1.2 and 1.7 ± 1.2, respectively. The mean preoperative and postoperative proximal CSA measurements were 16.4 ± 4.5 mm2 and 12.1 ± 3.9 mm2, respectively. The mean preoperative and postoperative distal CSA measurements were 13.6 ± 3.7 mm2 and 11.0 ± 3.1 mm2, respectively. A significant improvement was observed in VAS, BCTQ, and EDX 3 months after CTR. A weak, positive correlation was observed between the improvement in the BCTQ symptom severity and function subscales and CSAs following CTR. CONCLUSIONS: The results of this study demonstrate that preoperative median nerve CSA values may be used in evaluating CTR outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The effect of lighted toy on reducing pain and fear during blood collection in children between 3 and 6 years: A randomized control trial.

BACKGROUND: This study was carried out as an experimental research to determine the effect of the light toy on reducing pain and fear during blood collection in children. METHODS: The data were obtained 116 children. The "Interview and Observation Form Children's Fear Scale, Wong-Baker Faces, Luminous Toy and Stopwatch" was used for data collection. The data were evaluated using percentage, mean, standard deviation, chi-square, t-test, correlation analysis and Krusskal Wallis test in SPSS 21.0 package program. FINDINGS: The fear score average of the children in the lighted toy group was 0.95 ± 0.80, while it was 3.00 ± 0.74 in the control group. The difference between the groups in terms of the fear score average of the children was found statistically significant (p < 0.05). When the difference between groups in terms of pain status of children is examined, the pain level of children in the lighted toy group (2.83 ± 2.82,) was found to be significantly lower than the pain level of the children in the control group (5.86 ± 2.72) (p < 0.05). DISCUSSION: As a result of the study, it was found that the lighted toy given to the children during blood collection reduces their fear and pain levels. In the light of these findings, it is recommended to increase the use of lighted toys in blood collection. APPLICATION TO PRACTICE: The use of lighted toys as a distraction method during blood collection in children is an effective, easy-to-access and low-cost method. This method demonstrates that there is no need for expensive methods of distraction.

Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the CANDOR study.

CANDOR compared the safety/efficacy of carfilzomib with dexamethasone and daratumumab (KdD) to carfilzomib with dexamethasone (Kd) in adults with relapsed/refractory multiple myeloma (RRMM). This CANDOR subgroup analysis evaluated outcomes based on cytogenetic risk. Overall response rates (KdD vs. Kd) were 81% versus 56% in high-risk and 87% versus 79% in standard-risk groups. Median progression-free survival was 11.2 versus 7.4 months in high-risk (hazard ratio, 0.56 [95% CI, 0.34, 0.93]) and not reached versus 16.6 months in standard-risk groups (0.56 [95% CI, 0.39, 0.80]). These data support the efficacy of KdD in RRMM treatment, including in patients with high-risk cytogenetics.

Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis.

Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The phase III IKEMA study (clinicaltrials gov. Identifier: NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) versus Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate <60 mL/min/1.73 m². Addition of Isa prolonged progression-free survival (PFS) in patients with RI (hazard ratio: 0.27; 95% confidence interval [CI]: 0.11-0.66; median PFS not reached for Isa-Kd versus 13.4 months for Kd [20.8-month follow-up]). Complete renal responses occurred more frequently with Isa-Kd (52.0%) versus Kd (30.8%) and were durable in 32.0% versus 7.7% of patients, respectively. Treatment exposure was longer with Isa-Kd, with median number of started cycles and median duration of exposure of 20 versus 9 cycles and 81.0 versus 35.7 weeks for Isa-Kd versus Kd, respectively. Among patients with RI, the incidence of patients with grade ≥3 treatment-emergent adverse events was similar between the two arms (79.1% in Isa-Kd vs. 77.8% in Kd). In summary, the addition of Isa to Kd improved clinical outcomes with a manageable safety profile in patients with RI, consistent with the benefit observed in the overall IKEMA study population.

Multisystem inflammatory syndrome in children associated with COVID-19 in 101 cases from Turkey (Turk-MISC study).

AIM: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. METHODS: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. RESULTS: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 µg/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. CONCLUSION: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management.

Efficacy of erector spinae plane block on postoperative pain in patients undergoing lumbar spine surgery.

BACKGROUND: Major lumbar spine surgery causes severe pain in the postoperative period. There are few studies regarding the effect of erector spinae plane block (ESPB) effect on lumbar surgery and its effect is still controversial. Therefore, the study aimed to investigate the effect of ultrasound-guided low thoracic ESPB on opioid consumption and postoperative pain score. MATERIAL AND METHODS: Seventy-eight patients undergoing elective open lumbar spine surgery were randomized into two groups. In ESPB group (n = 35) received ultrasound-guided ESPB and in the control group (n = 35), there was no block. Postoperative opioid consumption as morphine equivalent dose, numerical rating scale, mobilization time, discharge time and side effects, bolus deliveries, rescue analgesia doses were evaluated. RESULTS: Total opioid consumption as morphine equivalent was higher in the control group than the ESPB group (p = 0.000). Compare with the control group, the numeric rating scale scores were lower in the ESPB group at the 6th, 12th, and 24th hours (p < 0.05). The patient-controlled analgesia button pressing number in the postoperative 24-h period was lower in the ESPB group (p = 0.000). In the postoperative 24-h period, the need for paracetamol in the ESPB group was lower and the difference between the groups was statistically significant (p = 0.008). Rescue analgesia (diclofenac) doses were higher in the control group (p < 0.05). There was no statistically significant difference in terms of side effects and mobilization times. CONCLUSION: ESPB is adequate for postoperative analgesia in patients undergoing lumbar spine surgery and can reduce opioid consumption compared with standard analgesia.

Safety and efficacy of obinutuzumab alone or with chemotherapy in previously untreated or relapsed/refractory chronic lymphocytic leukaemia patients: Final analysis of the Phase IIIb GREEN study.

The manageable toxicity profile of obinutuzumab (GA101; G) alone or with chemotherapy in first-line (1L; fit and non-fit) and relapsed/refractory (R/R) patients with chronic lymphocytic leukaemia (CLL) was established in the primary analysis of the Phase IIIb GREEN trial (Clinicaltrials.gov: NCT01905943). The final analysis (cut-off, 31 January 2019) is reported here. Patients received G (1000 mg) alone (G-mono; fit and non-fit patients) or with chemotherapy [fludarabine and cyclophosphamide (FC; fit patients); chlorambucil (non-fit patients); bendamustine (any patient)]. Study endpoints were safety (primary) and efficacy (secondary). Subgroup analyses were performed on prognostic biomarkers in 1L CLL. Overall, 630 patients received 1L and 341 received R/R CLL treatment. At the final analysis, no new safety signals were observed [Grade ≥ 3 adverse events (AEs): 1L 82·7%, R/R 84·5%; serious AEs: 1L 58·1%, R/R 62·5%]. Neutropenia (1L 50·5%, R/R 53·4%) and thrombocytopenia (1L 14·6%, R/R 19·1%) were the most common Grade 3-5 AEs. G-mono-, G-bendamustine and G-FC-treated patients with unmutated immunoglobulin heavy chain trended towards shorter progression-free survival. Achievement of minimal residual disease negativity was greatest in 1L patients treated with G-FC. In this final analysis of the GREEN trial, the safety profile of G was consistent with current risk management strategies. Biomarker analyses supported efficacy in the specific subgroups.

Evaluation of Hepatitis B screening and reactivation in patients receiving rituximab containing chemotherapy: A single-centre study.

AIMS: Hepatitis B virus (HBV) infection is a worldwide distributing viral disease. Hepatitis caused by HBV reactivation may progress to chronic illness and associated with increased risk of hepatic failure and hepatocellular cancer. Rituximab (RTX) is an immunosuppressive agent, is particularly used in the treatment of non-Hodgkin's Lymphoma. Patients have significant risk for HBV reactivation following chemotherapy with a RTX-containing regimen. This study aimed to determine the HBV screening manner and reactivation rates in patients with haematological neoplasm following chemotherapy including Rituximab. METHODS: This is a single-centered retrospective cohort study. A total of 331 adults with haematological disorders who received chemotherapy regimen including RTX between years of 2006 and 2016 were enrolled. Patients who experienced reactivation were evaluated. RESULTS: Only 130 of 331 patients were screened appropriately for HBV infection for 10-year period. We found 18 patients were Hepatitis B surface antigen (HBsAg) (+) and 16 (88.8%) of them received antiviral prophylaxis. Among screened patients, 27 were HBsAg (-)/AntiHBc (+) and only 10 (37%) of them received HBV prophylaxis. In total, nine patients experienced reactivation, six were from screened and three were from unscreened group. CONCLUSION: Incomplete screening and inappropriate prophylaxis may result in HBV reactivation in patients under RTX-based chemotherapy and related complications such as death.

Iatrogenic vascular laceration during posterior lumbar disc surgery: a literature review.

Iatrogenic vascular laceration is a rare but well-known complication of posterior lumbar disc surgery (PLUDS). We performed a review of the literature to evaluate the management of this life-threatening complication. A total of 54 papers containing 100 cases of vascular laceration following PLUDS between 1969 and 2018 were analyzed with our representative case with a left common iliac artery (CIA) laceration during a posterior approach for a far lateral L4-L5 disc herniation. There were 54 females and 35 males (12 cases with unreported gender) with ages ranging from 20 to 72 years. The most commonly involved spinal level was L4-L5 (n = 67). The duration from the causative surgery to the symptom of the vascular injury ranged from 0 to 50 h (mean, 7.3 h). Only 47.3% of patients underwent postoperative imaging and the most commonly injured vessel was the CIA (n = 49). Vascular repair, open surgery, and/or an endovascular procedure was performed in 95 patients. The most frequent complications were deep venous thrombosis in the leg and pulmonary emboli, where a complete recovery was seen in 75.3% of patients. The mortality rate was 18.8%. In hemodynamically unstable cases, an emergent exploratory laparotomy was life-saving even without vascular imaging, although angiography with/without endovascular intervention may be used in stable patients.

Ulnar nerve subluxation and dislocation: a review of the literature.

The pathogenesis of ulnar nerve subluxation and dislocation is widely debated. Upon elbow flexion, the ulnar nerve slips out of the groove for the ulnar nerve, relocates medial or anterior to the medial epicondyle, and returns to its correct anatomical position upon extension. This chronic condition can cause neuritis or neuropathy; however, it has also been suggested that it protects against neuropathy by reducing tension along the nerve. This article reviews the extant literature with the aim of bringing knowledge of the topic into perspective and standardizing terminology.

Sedoanalgesia Versus Infraclavicular Block for Closed Reduction of Pediatric Forearm Fracture in Emergency Department: Prospective Randomized Study.

OBJECTIVE: Procedural sedoanalgesia is commonly used in pediatric patients in the emergency department (ED) for interventional procedures, diagnosis, and treatment. However, this method causes serious systemic complications, such as respiratory and cardiac depression. To minimize these complications, ultrasound-guided regional anesthesia methods have been used in recent years. We aimed to compare the use of procedural sedoanalgesia (PSA) and infraclavicular block (ICB) in the pain management of pediatric patients who underwent closed reductions of forearm fractures. MATERIALS AND METHODS: This prospective, randomized, clinical study included patients aged 3 to 15 years who presented to the ED with forearm fractures. The patients were divided into 2 groups: the procedural sedoanalgesia group (group PSA, n = 30) and ultrasound-guided ICB group (group ICB, n = 30). Pain scores of the patients were evaluated using the Wong-Baker FACES Scale before and during the procedure. Pain scores and parental and operator satisfaction were compared between the groups. RESULTS: There was no statistical significance in terms of demographic data. The pain scores observed during the procedures were significantly higher in the group PSA than in the group ICB (3.07 ± 1.55 vs 0.47 ± 0.86, respectively; P < 0.001). The parental and operator satisfaction of the ICB group was significantly higher than that of the PSA group (P < 0.001). CONCLUSIONS: Ultrasound-guided ICB is a safe and effective method in the management of pain during closed reduction of forearm fracture in pediatric patients in EDs. It can be used safely in emergency rooms and has a high level of both parental and operator satisfaction.

Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey

Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28­87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10­40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1­55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.