Impact of Imatinib on reducing the painful crisis in patients with sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is a common hemoglobinopathy worldwide that causes painful crises and hospitalization of patients. These attacks decrease survival and cause chronic end-organ damage in these patients. HYPOTHESIS: For this reason, finding new treatment approaches could be helpful. METHOD: In this study, Imatinib was applied as a mast cell inhibitor to reduce pain crises in these patients. Seven patients resistant to hydroxyurea and folic acid treatment and who had at least four painful crises per year with hospitalization were enrolled in this study with treatment with Imatinib (100 mg, twice daily). Subsequently, the number and duration of hospitalizations, analgesic requirement, the severity of chronic pain, and changes in the hematological parameters of these patients were evaluated before and after the treatment. RESULTS: The data showed that the total number of hospitalizations and the entire duration of hospitalizations were reduced 16 times after treatment with Imatinib, without apparent changes in hematological parameters. Also, the demand for pethidine, tramadol, and nonsteroidal anti-inflammatory drugs (NSAIDs) was reduced in all patients. The average reduction in chronic pain was over 70%. CONCLUSION: This study demonstrates that treatment with Imatinib in patients with SCD or sickle cell anemia (SCA) may be a suitable therapeutic option for reducing painful crises.

Long-term follow-up of patients with hairy cell leukemia in the south of Iran.

BACKGROUND: Hairy cell leukemia (HCL) is an indolent chronic lymphoproliferative disorder and first-line treatment with either intravenous or subcutaneous cladribine generally leads to long-lasting remissions. METHOD: All 131 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 91 months. Data is from 2007 to 2020. We evaluated the response rate to cladribine as the first line and the response rate to cladribine with or without rituximab in relapsed patients. Further, we assessed relapse-free survival, complications, and secondary malignancy. RESULTS: After a median follow-up of 91 months, the recurrence rate was 24%. The 5-year and 10-year RFS rates were 85% and 66%, respectively. Adding rituximab to 2-CDA leads to a better response rate than just cladribine (90% vs. 27.3%, p-value = 0.002) in the relapsed patients. CONCLUSION: HCL patients have long-term survival when cladribine is the first line of treatment. Furthermore, adding rituximab to cladribine leads to a higher response rate.

Sildenafil for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: A Phase I/II Randomized Clinical Trial, SILDAT-TAHA6 Trial.

Background: Previous animal studies have shown a protective effect of 5-phosphodiesterase inhibitors on cancer therapeutics-related cardiac dysfunction (CTRCD) of anthracyclines. Aim: The aim of this study was to evaluate the clinical effect of sildenafil on the primary prevention of CTRCD in human. Materials and Methods: In this randomized double-blind clinical trial, the primary end point was efficacy in preventing the reduction of left ventricular ejection fraction (LVEF). The intervention group patients received sildenafil at a dose of 25 milligrams twice a day before starting the chemotherapeutic regimen, and the control group received placebo. All the patients at baseline and after the 6-month follow-up underwent 4D and speckle-tracking echocardiography and cardiac MRI, accompanied by hs-troponin I and NT-Pro-BNP measurement. Results: Sixty patients were enrolled in this study, and data from 52 patients (24 patients in the intervention group and 28 patients in the control group) were used in the final analysis. Our findings showed that in the intervention and control groups, LVEF was dropped from 61.28 ± 7.36 to 51.57 ± 7.67 (difference (D) = -9.71 ± 11.95, p=0.003) and from 57.9 ± 7.29 to 50.2 ± 7.02% (D = -7.7 ± 5.93; p=0.001), respectively (between-group difference = -2.01%, p=0.26). CTRCD was detected in 11 patients in the control group (42.8%) and 10 in the intervention group (41.6%, p=0.51). Conclusion: Consumption of sildenafil for primary prevention of anthracycline-induced cardiac toxicity seems to be unbeneficial. This trial is registered with IRCT20180506039554N1.

Bilateral Hypertrophic Olivary Degeneration as a Paraneoplastic Syndrome of a Poorly Differentiated Carcinoma of the Upper Gastrointestinal Tract: A Case Report and Literature Review.

INTRODUCTION: Hypertrophic olivary degeneration (HOD) is a unique form of trans-synaptic neuronal degeneration within the dentato-rubro-olivary pathway which is manifested by the enlargement and hyperintensities of the inferior olivary nucleus in the brain magnetic resonance imaging. CASE REPORT: We report a 53-year-old man admitted to our emergency department with a history of progressive ataxia and vertigo for 6 months before admission. Neurological examination revealed cerebellar dysfunction, and the brain magnetic resonance imaging showed bilateral HOD without an identifiable causative lesion within the brain or abnormal meningeal enhancement. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis, elevated protein, and negative cytology. Malignancy and paraneoplastic workup exhibited marked elevation of carbohydrate antigen 19-9 level and para-aortic lymphadenopathy. A histologic examination demonstrated the infiltration of lymph nodes by a malignant, poorly differentiated carcinomatous tumor that arises from the upper gastrointestinal tract. Considering the primary site of the tumor and HOD as a paraneoplastic effect of carcinoma, a FOLFIRINOX regimen, intravenous immunoglobulin, and pulse methylprednisolone were started. A follow-up imaging after 3 months depicted a significant resolution of HOD but the neurological status only mildly improved. The patient developed liver and adrenal metastasis over the following 6 months, culminating in his death. CONCLUSION: This study strengthens a relationship between HOD and malignancy as a paraneoplastic syndrome and provides a new incentive for further researches to confirm this association.

Effects of the Sufentanil and Dexmedetomidine Combination on Spinal Anesthesia in Patients Undergoing Lower Abdominal or Lower Extremity Surgery: A Double-Blind Randomized Controlled Trial.

Background: Intrathecal additive drugs are becoming increasingly common in anesthesia practice. We aimed to evaluate the additive effects of dexmedetomidine on spinal anesthesia with sufentanil in patients undergoing lower abdominal or lower limb surgery. Methods: This double-blind randomized controlled trial was performed in Mashhad, Iran, between 2017 and 2018. Sixty patients undergoing lower abdominal or lower limb surgery were randomly divided to receive 15 mg of bupivacaine and 3 µg of sufentanil (control group; n=30) or 15 mg of bupivacaine, 3 µg of sufentanil, and 10 µg of dexmedetomidine (intervention group; n=30). Outcomes, comprised of the onset and regression of sensory and motor blocks, the duration of analgesia, analgesic use, hemodynamic parameters, and side effects, were assessed. The data were analyzed in the SPSS software (version 22), using different statistical tests. A P value of less than 0.05 was considered significant. Results: The times of sensory and motor blocks reaching T10 and Bromage 3, respectively, were significantly shorter, while the times of sensory and motor regressions to S1 and Bromage 0, correspondingly, were significantly longer in the intervention group than in the control group (P<0.001). Both the frequency (P=0.006) and the dose (P<0.001) of postoperative analgesic use were significantly lower, and the duration of analgesia was significantly longer in the intervention group (P<0.001). The frequency of side effects and changes in hemodynamic parameters had no significant differences between the groups. Conclusion: The sufentanil and dexmedetomidine combination in spinal anesthesia caused the earlier onset and later regression of sensory and motor blocks, longer postoperative analgesia, and lower analgesic use without significant side effects or hemodynamic changes, which appears to be due to the combined effects of sufentanil and dexmedetomidine. Trial Registration Number: IRCT2017082833680N3.

Glucocorticoid induced diabetes and lipid profiles disorders amongst lymphoid malignancy survivors.

BACKGROUND AND AIMS: Hyperglycemia and glucose test abnormalities are problems during the treatment of patients with lymphoid malignancy, caused by corticosteroid therapy. However, its long-term complications or risk of developing diabetes are not available. METHODS: Two hundred patients with lymphoid hematologic malignancy were recruited and followed up for median of 47 months. The underlying hematologic malignancy includes Hodgkin's disease (HD), Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia(CLL), Multiple Myeloma (MM) and Acute Lymphocytic Leukemia (ALL). Fasting blood sugar, glucose tolerance test and lipid profiles were measured before each chemotherapy cycle and every 3 months after. This study was designed to evaluate patients for long-term follow up of glucose tests abnormalities. RESULTS: The mean age of the non-diabetic patients was significantly lower than that of diabetics and patients with fasting glucose disorder (p < 0.001). The prevalence of diabetes and impaired FBS and GTT was higher in NHL (9%), CLL (6.5%) and MM (1.5%), respectively. For lipid profiles, the highest levels of cholesterol and triglycerides were observed in multiple myeloma and the lowest in Hodgkin's lymphoma (P:0.004). CONCLUSIONS: The most important factor for steroid-induced diabetes is age, which was more prevalent with age increase (P < 0.001). Glucocorticoid-induced diabetes is common in multiple myeloma and then in chronic lymphocytic leukemia and non-Hodgkin's lymphoma in comparison with Hodgkin's lymphoma and acute lymphoblastic leukemia.

Opposing effects of external gibberellin and Daminozide on Stevia growth and metabolites.

Steviol glycosides (SVglys) and gibberellins are originated from the shared biosynthesis pathway in Stevia (Stevia rebaudiana Bertoni). In this research, two experiments were conducted to study the opposing effects of external gibberellin (GA3) and Daminozide (a gibberellin inhibitor) on Stevia growth and metabolites. Results showed that GA3 significantly increased the stem length and stem dry weight in Stevia. Total soluble sugar content increased while the SVglys biosynthesis was decreased by external GA3 applying in Stevia leaves. In another experiment, the stem length was reduced by Daminozide spraying on Stevia shoots. The Daminozide did not affect the total SVglys content, while in 30 ppm concentration, significantly increased the soluble sugar production in Stevia leaves. Although the gibberellins biosynthesis pathway has previously invigorated in Stevia leaf, the Stevia response to external gibberellins implying on high precision regulation of gibberellins biosynthesis in Stevia and announces that Stevia is able to kept endogenous gibberellins in a low quantity away from SVglys production. Moreover, the assumption that the internal gibberellins were destroyed by Daminozide, lack of Daminozide effects on SVglys production suggests that gibberellins biosynthesis could not act as a competitive factor for SVglys production in Stevia leaves.