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Efficacy and Safety of Blinatumomab for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Systemic Review and Meta-Analysis

Clin Lymphoma Myeloma Leuk. 2022 Dec 17:S2152-2650(22)01772-4. doi: 10.1016/j.clml.2022.12.009. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim was to evaluate the efficacy and safety of blinatumomab monotherapy for the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL).

METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched to collect clinical studies related to blinatumomab. The primary outcome measures were complete remission (CR), and minimal residual disease (MRD) response. Prognostic indicators included overall survival (OS) and relapse-free survival time (RFS). Grade ≥3 adverse reactions were mainly analyzed for safety, including cytokine release syndrome (CRS), neurological events and hematological toxicity. The heterogeneity was quantified by I2 statistic, which reflected the proportion of the true heterogeneity to the variance of the total effect size. Studies were considered heterogeneous if the I2 statistic was greater than 50%, and conversely, studies were homogeneous.

RESULTS: A total of 18 studies involving 1,373 patients were included. The analysis results showed a CR rate of 54% (95%CI:44%-64%) and an MRD response rate of 43% (95%CI:34%-51%). The CR rate was higher in patients with bone marrow (BM) blast <50% than in patients with BM blast ≥50% (71% vs. 34%). The median OS and RFS were 8.16 months (95%CI:6.64-9.69) and 6.02 months (95%CI:4.63-7.41), respectively. For safety analysis, the incidence of grade ≥3 adverse events (AEs) was 80% (95%CI:72%-88%), the incidence of grade ≥3 neurological toxicity was 7% (95%CI:4%-11%), and the incidence of grade ≥3 CRS was 3% (95%CI:2%-5%). However, the mixture of retrospective and prospective studies led to heterogeneity to some extent in this meta-analysis.

CONCLUSION: Blinatumomab is effective in the treatment of R/R B-ALL with a controlled occurrence of AEs and a reliable safety profile.

PMID:36593170 | DOI:10.1016/j.clml.2022.12.009

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Venous Reconstruction in Extremity Soft Tissue Sarcoma Is Not Essential

Vasc Endovascular Surg. 2023 Jan 2:15385744221150737. doi: 10.1177/15385744221150737. Online ahead of print.

ABSTRACT

OBJECTIVE: Limb salvage is an important concern following complete oncologic resection for extremity soft tissue sarcoma (STS). Vascular reconstruction is essential for limb salvage. The purpose of this study was to evaluate the outcomes of vascular reconstruction in patients with extremity STS.

METHODS: This is a retrospective, multi-center, case series of consecutive patients who underwent vascular reconstruction during extremity STS resection at 2 major centers in Korea. Demographics, reconstruction methods, type of conduit, surgical complications, graft patency, limb salvage rate, and patient survival were reviewed.

RESULTS: From March 2005 to December 2020, 43 patients underwent vascular reconstructions during STS resection. Among the patients, 22 (51.2%) received arterial only, and 21 (48.8%) received simultaneous arterial and venous reconstructions. For the types of conduits, autologous saphenous veins (56.2%), artificial grafts (26.3%), and cryopreserved allografts (15.8%) were used. During a median follow-up of 23.8 months (interquartile range; 7.7-54.5), the overall primary patency of the reconstructed vessels was significantly higher in arteries than in veins (82.5% vs 56.3% at 12 months, P < .001). According to the type of conduit, the primary patency rate of autogenous vein seemed higher in venous reconstruction, however, there was no statistical significance in both arterial and venous reconstruction. There was no significant difference in primary arterial patency rate (P = .132) or incidence of surgical complications including postoperative edema or wound problem whether or not simultaneous venous reconstruction was performed with arterial reconstruction. The overall limb salvage rate and patient survival were 97.4%, 95.1%, and 89.4% and 91.9%, 81.7%, and 65.4% at 12, 24, and 36 months, respectively.

CONCLUSIONS: Patency rates were poorer in venous reconstruction than in arterial reconstruction. In terms of arterial patency and postoperative complication, the role of simultaneous arterial and venous reconstruction seems not essential, however, it needs to be evaluated in future studies.

PMID:36592476 | DOI:10.1177/15385744221150737

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Arterial Blood Supply of the Mesosalpinx Appears Segmentally Organized in Absence of Uterine Tubes Arteries

Physiol Res. 2022 Dec 27;71(Suppl 1):S107-S113.

ABSTRACT

Arterial branches to the uterus and ovaries that pass through the mesosalpinx contribute significantly to the maintenance of the ovarian reserve. Especially arterial supply of the uterine tube is provided by a number of anastomoses between both the uterine and ovarian vessels. Knowledge on the morphologic peculiarities will allow to identify main contributors especially blood flow ultrasound examination for the purpose of ovary preserving surgery. This study aimed at identifying landmarks especially for so-called low-flow tubal vessels. Arteries of 17 female Thiel-embalmed bodies were studied along three preselected paramedian segments and measurements taken. A section was made through the center of the ovary perpendicular to uterine tube, then the mesosalpinx tissue distance was divided into 3 equivalent zones: upper, middle and lower thirds. The surface area of the mesosalpinx averaged 1088 ± 62 mm2. 47.7 ± 7.1 % of the mesosalpinx zones included macroscopically visible vessels. The lower third segment of mesosalpinx was the thickest averaging 2.4 ± 1.5 mm. One to three tubal branches were identified in the middle third of the mesosalpinx. Arterial anastomoses were found in the upper segment of the mesosalpinx, but no presence of a marginal vessel supplying the fallopian tube could be found. Statistically significant moderate positive correlations were established between the diameters of the mesosalpingeal arteries between the three zones. The mesosalpinx, uterine tube and the ovary form areas of segmental blood supply. Variants of tubal vessels appear to be a sparse source of blood supply.

PMID:36592446

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Uterine Natural Killer Cells in the Context of Implantation: Immunohistochemical Analysis of Endometrial Samples from Women with Habitual Abortion and Recurrent Implantation Failure

Physiol Res. 2022 Dec 27;71(Suppl 1):S99-S105.

ABSTRACT

Infertility affects approximately 48 million couples globally. Despite the enormous progress of the methods of reproductive medicine that has been made since the first test-tube baby was born in 1978, the implantation rate of day-3 embryos is only around 15-20 % and 30 % of day-5 embryos. Numerous strategies aim to improve implantation rates and prevent repeated implantation failure, however there is no specific general recommendation leading to satisfying results. One of the many risk factors relevant in this regard is the uterine immunological make-up, mainly the uterine Natural Killer (uNK) cells. They orchestrate the overall immune response during implantation by influencing trophoblast invasion and vascular remodeling and throughout pregnancy, uNK cells are also the main immune cells at the maternal-foetal interface. Previously, uNK count has been correlated with various fertility issues including idiopathic reccurent miscarriage. The present study used endometrial samples collected from 256 patients with recurrent implantation failure (RIF), habitual abortion (HA) and idiopathic sterility. Samples were collected between day 19 and 21 of the menstrual cycle mainly by Pipelle endometrial sampling. The samples were fixed in formalin for 24 hours and further processed for immunohistochemistry using anti-CD56 to visualize this antigen marker of uNK cells. Immunohistochemical counting was performed to assess the low, normal, or elevated count of uNK cells. According to the one-way ANOVA test, the age of our patients did not have any influence on the count of uNK cells. With Spearman correlation analysis, we found statistically significant correlation (p-value 0.05) of -0.133 between prior miscarriage and lower uNK cell count. Using the same analysis we found statistically significant correlation (correlation 0.233 with p-value 0.01) between number of uNK cells and activation status. Patients with higher uNK cells were more frequenty diagnosed with endometriosis (p-value 0.05, correlation 0.130). Patients with an immunological factor of sterility (defined by a clinical immunologist) had a lower chance of gravidity (-0.203 with p-value 0.01). Based on our results, we can confirm that there is a correlation between RIF, HA, idiopathic sterility, endometriosis, and immunological factor of sterility (uNK cell count). The true predictive value with regard to fertility outcomes needs to be addressed in future research.

PMID:36592445

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Clinical lipidomics in the era of the big data

Clin Chem Lab Med. 2023 Jan 4. doi: 10.1515/cclm-2022-1105. Online ahead of print.

ABSTRACT

Lipidomics as a branch of metabolomics provides unique information on the complex lipid profile in biological materials. In clinically focused studies, hundreds of lipids together with available clinical information proved to be an effective tool in the discovery of biomarkers and understanding of pathobiochemistry. However, despite the introduction of lipidomics nearly twenty years ago, only dozens of big data studies using clinical lipidomics have been published to date. In this review, we discuss the lipidomics workflow, statistical tools, and the challenges of standartisation. The consequent summary divided into major clinical areas of cardiovascular disease, cancer, diabetes mellitus, neurodegenerative and liver diseases is demonstrating the importance of clinical lipidomics. In these publications, the potential of lipidomics for prediction, diagnosis or finding new targets for the treatment of selected diseases can be seen. The first of these results have already been implemented in clinical practice in the field of cardiovascular diseases, while in other areas we can expect the application of the results summarized in this review in the near future.

PMID:36592414 | DOI:10.1515/cclm-2022-1105

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Outcomes of cyanoacrylate closure of the truncal varicose vein insufficiency: A comparison between young and elderly patients

Phlebology. 2023 Jan 2:2683555221150147. doi: 10.1177/02683555221150147. Online ahead of print.

ABSTRACT

OBJECTIVES: Cyanoacrylate closure (CAC) procedure has become an alternative treatment method that has become increasingly popular in the treatment of chronic venous insufficiency (CVI) in recent years. The present study was designed to assess the feasibility, tolerance, results, and efficacy of CAC for truncal varicosities in elderly population.

METHODS: In this retrospective single-center observational cohort study, CAC procedure was performed in 160 patients (184 limbs) with truncal varicose vein insufficiency. The patients were divided into two groups: elderly group, and younger group. The primary outcome of this study was to assess the feasibility, tolerance, and safety of the CAC procedure for truncal varicosities in elderly population over 70 years. The Venous Clinical Severity Score (VCSS), visual analogue scale of pain (VASP) and occlusion rate of the treated target veins of the patients were evaluated and compared among groups. The secondary outcomes were to evaluate and compare technical success, mortality, major adverse events, and other postoperative complications between the groups.

RESULTS: All operations were carried out under local anesthesia. There were no technical failures or device-related complications. Anatomic success rate was 100% after procedures. The occlusion rate for the elderly group at 2 weeks, 6 months, and 12 months was 100%, 92.3%, and 92.3%, respectively, while the occlusion rate for the younger group was 100%, 97%, and 94.7%, respectively. There was no significant difference in occlusion rates between two groups (p > .05) (Log Rank = 0,231). Improvement in the VCSSs was statistically significant between baseline and 12 months after procedure in both groups (p < .001). Improvement in the VASPs was statistically significant between baseline and 2 weeks after procedure in both groups (p < .001). There were no symptoms or signs of sural nerve injury, hematoma, or phlebitis in either group.

CONCLUSIONS: Although it has some potential risks, it is conceivable that the CAC procedure may be applied in selected fit elderly patients for the treatment of CVI. Age appeared to have no effect on the early and mid-term prognosis of the CAC procedure performed in the study cohort.

PMID:36592404 | DOI:10.1177/02683555221150147

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Trends in suicide methods in Switzerland from 1969 to 2018: an observational study

Swiss Med Wkly. 2022 Dec 10;152:40007. doi: 10.57187/smw.2022.40007.

ABSTRACT

BACKGROUND: Suicide is a serious societal and health problem. We examined changes in rates of completed suicides in Switzerland between 1969-2018 with particular regard to different methods of suicide used in different subgroups of the resident population.

METHODS: We used data of the Swiss cause of death statistics and Poisson regression models to analyse annual incidence rates and calendar time trends of specific suicide methods used in population subgroups by sex (men vs women), age (10-29, 30-64, >64 years), and nationality (Swiss vs other citizenship).

RESULTS: There were 64,996 registered suicides between 1969 and 2018. Across these 5 decades, the overall suicide rate was higher in men than in women (incidence rate ratio [IRR] 2.62, 95% confidence interval [CI] 2.58-2.67), in Swiss citizens than in foreigners (IRR 2.02; 95% CI 1.97-2.07), and in older residents (>64 years) than in the age groups 30-64 years (IRR 1.35, 95% CI 1.32-1.37) and 10-29 years (IRR 2.37, 95% CI 2.32-2.43). After peaking in the 1980s, the overall suicide rate had declined in all of these population subgroups, with flattening trends over most recent years. The most common specific methods of suicide were hanging (accounting for 26.7% of all suicides) and firearms (23.6%). The rates of the specific suicide methods were usually higher in men, in Swiss citizens and in older residents, and they had typically declined over most recent decades in the population subgroups examined. However, some methods diverged from this general pattern, at least in some population subgroups. For instance, railway suicides most recently increased in younger and in male residents whereas suicides by gas and by drowning were only at a low level after rapid declines in the last millennium.

CONCLUSIONS: Restricting access to lethal means (e.g., detoxification of domestic gas), improvements in health care and media guidelines for responsible reporting of suicides are possible explanations for the generally declining suicide rates in Switzerland. Whereas some methods (e.g., poisoning by gases or drowning) had become rare, others continue to account for many suicides every year, at least in some population subgroups (e.g., firearms in older Swiss men or railway suicides in younger and in male residents). As different methods of suicide are chosen by different people or subgroups of the population, preventive efforts should include differentiated strategies and targeted measures to further reduce suicides in Switzerland and elsewhere.

PMID:36592392 | DOI:10.57187/smw.2022.40007

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Long noncoding RNA HOTAIR and Midkine as biomarkers in thyroid cancer

Egypt J Immunol. 2023 Jan;30(1):96-104.

ABSTRACT

Thyroid cancer is the most common endocrine malignancy, and its incidence is increasing. Differentiated thyroid cancer is the most common type and papillary thyroid carcinoma is the most common type of differentiated thyroid cancer. This work aimed to study long noncoding (Lnc) RNA homeobox transcript antisense RNA (HOTAIR) expression in plasma and serum midkine, a heparin binding growth factor, as biomarkers of thyroid cancer. This study included 27 thyroid cancer patients, 29 patients with benign thyroid disease and 26 individuals as normal controls. HOTAIR expression was assessed by real time polymerase chain reaction and midkine by ELISA. These biomarkers were elevated in thyroid cancer patients than patients with benign thyroid diseases and controls. Patients with thyroid cancer stage III had higher midkine levels in comparison to those with stage-I and stage-II (p < 0.001). Patients with grade II had higher midkine in comparison to those with grade I (p < 0.001). Statistically significant elevation of HOTAIR expression was found in stage III and stage II (p=0.001), compared to stage I. However, no difference was observed between stage II and stage III (p=0.533). There was no difference in both biomarkers in different histopathological types of thyroid cancer. ROC analysis was used for detection of thyroid cancer, midkine had AUC of 0.95 at a cutoff 897.5 pg/ml with a sensitivity of 98.0%, and specificity of 81.5% (p < 0.001). HOTAIR had AUC of 1 at a cutoff 11.8-fold change with a sensitivity and specificity of 100 %, (p < 0.001). We concluded that HOTAIR has high sensitivity and specificity in detection of thyroid cancer. It was correlated with tumor stage but not with histopathological types.

PMID:36592390

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The role of pain-related disability on treatment outcome and psychosocial symptoms in patients with temporomandibular disorders – a pilot study

Acta Odontol Scand. 2023 Jan 2:1-6. doi: 10.1080/00016357.2022.2162575. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of the pilot study was to investigate the association of pain-related disability with the outcome of conservative treatment of temporomandibular disorders (TMD) and with depressive and non-specific physical symptoms among TMD pain patients utilizing Graded Chronic Pain Scale 1.0 (GCPS1.0) as a screening instrument.

MATERIAL AND METHODS: The study included 80 adult patients who were referred to the Oral and Maxillofacial Department, Oulu University Hospital, Finland, due to TMD pain. At baseline, pain-related disability was assessed by using the GCPS1.0 according to the Research Diagnostic Criteria for TMD (RDC/TMD), and the patients were categorized into three TMD subtypes, 1-3. Patients were given conservative TMD treatment. At follow-up visits (1, 3, 6, and 12 months), patients evaluated the pain intensity on an NRS and described the treatment outcome and the severity of the TMD symptoms on a numerical scale.

RESULTS AND CONCLUSIONS: Patients with TMD subtype 3 (moderate/severe disability) had the highest NRS scores and described their symptoms as most severe at each time point, statistically significantly so at 1-month and 6-month follow-up (p < .05). The highest proportion of depressive symptoms was found in TMD subtype 3 (p < .05). The current pilot study showed that moderate/severe TMD-related disability, based on the GCPS 1.0 as a screening tool, may be linked with poor treatment outcome and depressive symptoms. Studies with larger samples are needed to confirm the results.

PMID:36592379 | DOI:10.1080/00016357.2022.2162575

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Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on the Outcomes of Patients With Metastatic Pancreatic Adenocarcinoma (MPA) During First-Line Treatment With FOLFIRINOX: A Single-Center Retrospective Analysis

Cancer Control. 2023 Jan-Dec;30:10732748221149543. doi: 10.1177/10732748221149543.

ABSTRACT

INTRODUCTION: The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP.

METHODS: This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models.

RESULTS: The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 – 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 – .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 – .80; P = .005), PP was associated with statistically superior OS.

CONCLUSIONS: Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.

PMID:36592369 | DOI:10.1177/10732748221149543