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BMC Nephrology Oct 2023Castleman's disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated...
BACKGROUND
Castleman's disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated immunological dysfunction. ImmunoglobulinG4-related disease (IgG4-RD) is a collection of systemic disorders that affect numerous organs and are also referred to as IgG4-associated sclerosing diseases. CD and IgG4-RD are difficult to separate because they may manifest similar commin clinical features.
CASE PRESENTATION
This case describes a 53-year-old female who, during routine medical check-up, exhibited a progressive increase in serum globulin levels and a simultaneous worsening of anemia symptoms, raising concern for a clonal plasma cell disease such as myeloma. However, bone marrow punctures did not reveal any abnormal plasma cells. Also, serum and urine immunofixation electrophoresis demonstrated no abnormal monoclonal protein bands. In addition, several laboratory findings excluded chronic liver disease, chronic infections caused by bacteria or viruses. Later, we found elevated serum IgG4 levels (10,700 mg/L), and identified multiple enlarged lymph nodes throughout the patient's body. Axillary lymph node aspiration revealed no abnormal lymphocytes, ruling out the possibility of lymphoma. Pathological morphology of the axillary lymph revealed a large number of plasma cells in the lymphatic follicles. In addition, there was a reduction in lymphatic follicle size and apoptosis of the germinal centres. Immunohistochemistry revealed IgG4+/IgG + in > 40% of cells, and more than 100 IgG4 + cells per high powered field (HPF) of specimen. As of now, finding strongly suggested IgG4-RD. This patient was treated with glucocorticoids and various immunosuppressive drugs, such as prednisone, cyclosporine, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine and hydroxychloroquine. Unfortunately, the patient did not recover. Ultimately, idiopathic multicentric Castleman disease (iMCD) was diagnosed in relation to the patient's clinical presentation and laboratory tests, and after combination chemotherapy (VCD: Bortezomib, Cyclophosphamide and Dexamethasone), durable remission was achieved without serious adverse effects. During the follow-up period of one year and ten months, the patient remained stable.
CONCLUSION
The diagnosis of Castleman must be distinguished from other disorders such as IgG4-RD, malignant lymphoma, reactive hyperplasia of various lymph nodes (mostly caused by viral infections), plasmacytoma, advanced HIV and rheumatic diseases. Besides observing systemic symptoms, laboratory tests such as immunoglobulin levels, complement levels, interleukin levels, and C-reactive protein levels should also be performed in order to determine a diagnosis.
Topics: Female; Humans; Middle Aged; Castleman Disease; Immunoglobulin G4-Related Disease; Bortezomib; Immunoglobulin G; Cyclophosphamide
PubMed: 37784011
DOI: 10.1186/s12882-023-03335-7 -
Journal of Pharmacy Practice Aug 2023: Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality especially among diabetes mellitus (DM) patients. Effective treatments against COVID-19... (Review)
Review
: Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality especially among diabetes mellitus (DM) patients. Effective treatments against COVID-19 can complement the vaccination effort worldwide. Many review articles studied the effects of the dipeptidyl peptidase 4 (DPP-4) inhibitors among COVID-19 patients and found conflicting results. This heterogeneity may be due to different systemic pleiotropic effects of different DPP-4 inhibitors. Sitagliptin appears to be one of the good DPP-4 inhibitors that have antiinflammatory and antithrombotic effect. Therefore, this review assessed the benefits and safety of sitagliptin in the treatment of COVID-19. : A detailed literature review using the electronic databases of Pubmed and Google Scholar was conducted during July and August 2021 to find out studies that published in English language and discussed the role of sitagliptin for COVID-19 patients. : 14 articles were eligible and thus included in this narrative review. Nine of these articles agreed to the benefit of sitagliptin in the treatment of COVID-19, while 3 studies considered sitagliptin as non useful or even risky, and one study was neutral in its conclusion towards the usage of sitagliptin in COVID-19. Only one study focused on the safety of sitagliptin and found that it is safe. : Sitagliptin has anti-inflammatory, antifibrotic and antiapoptotic properties; such effects may be beneficial in reducing risks of COVID-19. Sitagliptin has good safety and fair benefits to reduce mortality among DM patients with COVID-19. Further randomized clinical trials are needed to confirm these benefits especially among patients without DM.
Topics: Humans; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Diabetes Mellitus, Type 2; COVID-19; Treatment Outcome
PubMed: 35581701
DOI: 10.1177/08971900221102119 -
Hematology (Amsterdam, Netherlands) Dec 2023Although multiple myeloma is still incurable, an abundance of novel treatments have become available for relapsed and or refractory multiple myeloma (RRMM). Direct... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although multiple myeloma is still incurable, an abundance of novel treatments have become available for relapsed and or refractory multiple myeloma (RRMM). Direct head-to-head comparisons between the novel treatments are lacking. We performed a network meta-analysis to evaluate immediate effects such as response quality of current novel-drugs combined therapeutic regimens, with the aim to identify treatments that could be more effective than others in RRMM.
METHODS
We searched Cochrane Library, PubMed, Embase, and Web of Science for randomized controlled clinical trials receiving novel-drugs combined treatments as means of interventions. The primary endpoint was objective response rates (ORRs). We used the surface under the cumulative ranking curve (SUCRA) to sequence treatments. Totally, 22 randomized controlled trials were identified for final evaluation. With the aim to include all regimens within one network analysis, we divided the treatment schemes into 13 categories according to the use of novel drugs.
RESULTS
Carfilzomib-, daratumumab-, and isatuximab-based treatments had better ORRs than bortezomib combined dexamethasone and lenalidomide combined dexamethasone. Daratumumab- and isatuximab-based treatments had better ORRs than pomalidomide combined dexamethasone. According to the SUCRA, daratumumab- and isatuximab-based triple-drug regimens had higher probabilities of achieving better ORRs, followed by carfilzomib, elotuzumab, venetoclax, selinexor, ixazomib, vorinostat, pomalidomide, panobinostat, lenalidomide.
CONCLUSIONS
Our network meta-analysis performed a complete review of the ORRs of all current available novel-drugs based regimens for RRMM. By using the clinical data all from randomized controlled studies, daratumumab- and isatuximab-based treatments were identified to be the best treatments receiving better response quality.
Topics: Humans; Multiple Myeloma; Lenalidomide; Network Meta-Analysis; Bortezomib; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37343159
DOI: 10.1080/16078454.2023.2225342 -
The Indian Journal of Tuberculosis Oct 2023Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The... (Review)
Review
INTRODUCTION
Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol.
MATERIALS AND METHODS
We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review.
RESULTS
Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment.
DISCUSSION
ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management.
CONCLUSION
This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.
Topics: Humans; Rifampin; Antitubercular Agents; Pyrazinamide; Isoniazid; Thrombocytopenia
PubMed: 37968056
DOI: 10.1016/j.ijtb.2023.04.029 -
Journal of Hematology & Oncology Jul 2023Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in...
Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Europe; Lenalidomide; Multiple Myeloma
PubMed: 37468911
DOI: 10.1186/s13045-023-01474-w -
Brain : a Journal of Neurology Mar 2024Progress in the development of effective chemotherapy is producing a growing population of patients with acute and chronic painful chemotherapy-induced peripheral...
Progress in the development of effective chemotherapy is producing a growing population of patients with acute and chronic painful chemotherapy-induced peripheral neuropathy (CIPN), a serious treatment-limiting side effect for which there is currently no US Food and Drug Administration-approved treatment. CIPNs induced by diverse classes of chemotherapy drugs have remarkably similar clinical presentations, leading to the suggestion they share underlying mechanisms. Sensory neurons share with immune cells the ability to detect damage associated molecular patterns (DAMPs), molecules produced by diverse cell types in response to cellular stress and injury, including by chemotherapy drugs. DAMPs, in turn, are ligands for pattern recognition receptors (PRRs), several of which are found on sensory neurons, as well as satellite cells, and cells of the immune system. In the present experiments, we evaluated the role of two PRRs, TLR4 and RAGE, present in dorsal root ganglion (DRG), in CIPN. Antisense (AS)-oligodeoxynucleotides (ODN) against TLR4 and RAGE mRNA were administered intrathecally before ('prevention protocol') or 3 days after ('reversal protocol') the last administration of each of three chemotherapy drugs that treat cancer by different mechanisms (oxaliplatin, paclitaxel and bortezomib). TLR4 and RAGE AS-ODN prevented the development of CIPN induced by all three chemotherapy drugs. In the reversal protocol, however, while TLR4 AS-ODN completely reversed oxaliplatin- and paclitaxel-induced CIPN, in rats with bortezomib-induced CIPN it only produced a temporary attenuation. RAGE AS-ODN, in contrast, reversed CIPN induced by all three chemotherapy drugs. When a TLR4 antagonist was administered intradermally to the peripheral nociceptor terminal, it did not affect CIPN induced by any of the chemotherapy drugs. However, when administered intrathecally, to the central terminal, it attenuated hyperalgesia induced by all three chemotherapy drugs, compatible with a role of TLR4 in neurotransmission at the central terminal but not sensory transduction at the peripheral terminal. Finally, since it has been established that cultured DRG neurons can be used to study direct effects of chemotherapy on nociceptors, we also evaluated the role of TLR4 in CIPN at the cellular level, using patch-clamp electrophysiology in DRG neurons cultured from control and chemotherapy-treated rats. We found that increased excitability of small-diameter DRG neurons induced by in vivo and in vitro exposure to oxaliplatin is TLR4-dependent. Our findings suggest that in addition to the established contribution of PRR-dependent neuroimmune mechanisms, PRRs in DRG cells also have an important role in CIPN.
Topics: Humans; United States; Animals; Rats; Bortezomib; Oxaliplatin; Toll-Like Receptor 4; Neuralgia; Sensory Receptor Cells; Oligodeoxyribonucleotides; Paclitaxel; Antineoplastic Agents
PubMed: 37787114
DOI: 10.1093/brain/awad339 -
Cardiovascular Diabetology Feb 2024SGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
SGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other clinical parameters.
METHODS
This is a multicenter, open-label, randomized, controlled trial. Patients with type 2 diabetes (20-74 years old) with HbA1c levels of 7.0-10.5% and serum triglyceride levels of 120-399 mg/dL (1.35-4.50 mmol/L) on diet and/or oral hypoglycemic agents were enrolled. Subjects were randomized to treatment with ipragliflozin (50 mg/day, n = 77) or sitagliptin (50 mg/day, n = 83). Laboratory measurements were performed at 0, 1, 3, and 6 months of treatment.
RESULTS
Ipragliflozin and sitagliptin reduced fasting plasma glucose, glycoalbumin, and HbA1c almost equally. Ipragliflozin increased HDL-C and decreased apo E. Sitagliptin decreased TG, apo B48, CII, and CIII, but increased LDL-C. The between-treatment differences were significant for HDL-C (P = 0.02) and apo B48 (P = 0.006), and nearly significant for apo A1 (P = 0.06). In addition, ipragliflozin reduced body weight, blood pressure, serum liver enzymes, uric acid, and leptin, and increased serum ketones compared with sitagliptin.
CONCLUSIONS
While ipragliflozin and sitagliptin showed similar effects on glycemic parameters, the effects on serum lipid and apolipoprotein profiles were different. Ipragliflozin may have an anti-atherogenic effect through modulation of HDL-C and apo E compared to sitagliptin through TG and apo B48, CII, and CIII in patients with type 2 diabetes.
Topics: Adult; Aged; Humans; Middle Aged; Young Adult; Apolipoproteins; Apolipoproteins E; Blood Glucose; Diabetes Mellitus, Type 2; Glucosides; Glycated Hemoglobin; Hypoglycemic Agents; Sitagliptin Phosphate; Thiophenes
PubMed: 38331780
DOI: 10.1186/s12933-024-02149-7 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914 -
Molecules (Basel, Switzerland) Nov 2023Pyrazine is a six-membered heterocyclic ring containing nitrogen, and many of its derivatives are biologically active compounds. References have been downloaded through... (Review)
Review
Pyrazine is a six-membered heterocyclic ring containing nitrogen, and many of its derivatives are biologically active compounds. References have been downloaded through Web of Science, PubMed, Science Direct, and SciFinder Scholar. The structure, biological activity, and mechanism of natural product derivatives containing pyrazine fragments reported from 2000 to September 2023 were reviewed. Publications reporting only the chemistry of pyrazine derivatives are beyond the scope of this review and have not been included. The results of research work show that pyrazine-modified natural product derivatives have a wide range of biological activities, including anti-inflammatory, anticancer, antibacterial, antiparasitic, and antioxidant activities. Many of these derivatives exhibit stronger pharmacodynamic activity and less toxicity than their parent compounds. This review has a certain reference value for the development of heterocyclic compounds, especially pyrazine natural product derivatives.
Topics: Pyrazines; Chemistry, Pharmaceutical; Anti-Inflammatory Agents; Anti-Bacterial Agents; Biological Products
PubMed: 37959859
DOI: 10.3390/molecules28217440 -
Frontiers in Endocrinology 2023As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a Bayesian network meta-analysis was conducted to evaluate the efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus (T2DM).
METHODS
We systematically searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing teneligliptin with placebo or active comparators in T2DM patients for at least 12 weeks were included in the study. Data analysis was performed using R 4.2.3 and Stata 17.0 software. Each outcome was presented as a mean difference (MD) or an odds ratio (OR) along with 95% confidence interval (CI) and the surface under the cumulative ranking curve value (SUCRA).
RESULTS
A total of 18 RCTs with 3,290 participants with T2DM were included in this study. Generally, compared to placebo, sitagliptin, vildagliptin, metformin, and bromocriptine, 20 mg of teneligliptin showed better efficacy in reducing HbA1c (MD [95% CI], -0.78 [-0.86 to -0.70], -0.08 [-0.36 to 0.19], -0.04 [-0.72 to 0.60], -0.12 [-0.65 to 0.42], and -0.50 [-0.74 to -0.26], respectively) and fasting plasma glucose (FPG) (MD [95% CI], -18.02 [-20.64 to -15.13], 1.17 [-9.39 to 11.70], -8.06 [-30.95 to 14.35], -2.75 [-18.89 to 13.01], and -34.23 [-45.93 to -22.96], respectively), and 40 mg of teneligliptin also showed better efficacy in reducing HbA1c (MD [95% CI], -0.84 [-1.03 to -0.65], -0.15 [-0.49 to 0.19], -0.10 [-0.81 to 0.57], -0.18 [-0.76 to 0.39], and -0.56 [-0.88 to -0.26], respectively) and FPG (MD [95% CI], -20.40 [-26.07 to -14.57], -1.20 [-13.21 to 10.38], -10.43 [-34.16 to 12.65], -5.13 [-22.21 to 11.66], and -36.61 [-49.33 to -24.01], respectively). Compared to placebo, 20 mg of teneligliptin showed no significant difference in incidences of hypoglycemia and gastrointestinal adverse events (OR [95% CI], 1.30 [0.70 to 2.19] and 1.48 [0.78 to 2.98], respectively), and 40 mg of teneligliptin showed no significant difference in incidence of hypoglycemia (OR [95% CI], 2.63 [0.46 to 8.10]). Generally, antidiabetic effect and hypoglycemia risk of teneligliptin gradually increased as its dose increased from 5 mg to 40 mg. Compared to 20 mg of teneligliptin, 40 mg of teneligliptin showed superior efficacy and no-inferior safety, which was considered as the best option in reducing HbA1c, FPG, and 2h PPG and increasing proportion of the patients achieving HbA1c < 7% (SUCRA, 85.51%, 84.24%, 79.06%, and 85.81%, respectively) among all the included interventions.
CONCLUSION
Compared to sitagliptin, vildagliptin, metformin, bromocriptine, and placebo, teneligliptin displayed favorable efficacy and acceptable safety in treating T2DM. Twenty milligrams or 40 mg per day was the optimal dosage regimen of teneligliptin. The results of this study will provide important evidence-based basis for rational use of teneligliptin and clinical decision-making of T2DM medication.
Topics: Humans; Bromocriptine; Glycated Hemoglobin; Network Meta-Analysis; Vildagliptin; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate; Hypoglycemic Agents; Hypoglycemia
PubMed: 38189048
DOI: 10.3389/fendo.2023.1282584