Received Combination Therapy Research Articles

Anticancer-Drug-Related Cardiotoxicity from Adjuvant Goserelin and Tamoxifen Therapy

Background: Breast cancer is a prevalent malignancy with rising incidence globally. Advances in endocrine therapy have improved outcomes for premenopausal women with hormone receptor-positive breast cancer. However, these treatments may induce menopause-like states, potentially elevating cardiovascular risks, including left ventricular (LV) dysfunction. This study aims to evaluate the impact of one year of adjuvant endocrine therapy with goserelin and tamoxifen on LV function in premenopausal breast cancer patients. Methods: The ISACS cardiovascular toxicity (NCT01218776) is a pilot multicenter registry of breast cancer patients referred to hospitals for routine surveillance, suspected, or confirmed anticancer-drug-related cardiotoxicity (ADRC). Patients may be enrolled retrospectively (1 year) and prospectively. The pilot phase focused on the available data on combined goserelin and tamoxifen therapy for breast cancer and its impact on LV disfunction at 1-year follow-up. Inverse probability of treatment weighting (IPTW) analysis of the ISACS registry was performed assigning 70 patients to combined endocrine therapy (goserelin and tamoxifen). Controls consisted of 120 patients with no adjuvant combined goserelin and tamoxifen therapy. None of the patients developed distant metastasis. Primary outcome measures were as follows: low LV function in women as defined by a left ventricular ejection fraction (LVEF) < 65% and subclinical LV dysfunction as defined by a 10-percentage point decrease in LVEF. Results: In the overall population, combined goserelin and tamoxifen therapy did not affect the mean LV function compared with controls at 3-, 6-, and 12-month follow-up (65.7 ± 2.7% versus 65.3 ± 2.1%, p value = 0.27; 65.5 ± 2.9% versus 65.1 ± 2.5%, p value = 0.34; 65.0 ± 3.2% versus 64.6 ± 3.1%, p value = 0.29, respectively). The mean LVEF reduction in patients who did or did not receive combination therapy for 12 months was small and approximately similar (1.03 ± 2.5% versus 1.16 ± 2.9%, p value = 0.73). Using IPTW analyses, there were no significant associations between combined therapy and low LV function (risk ratio [RR]: 1.75; 95% CI: 0.71–4.31) or subclinical LV dysfunction (RR: 1.50; 95% CI: 0.35–6.53) compared with controls. Conclusions: One year of endocrine therapy with goserelin and tamoxifen does not cause ADRC in patients with invasive breast cancer. Findings are independent of the severity of the disease. Results may not be definitive without replication in studies with larger sample size.

Early initiation of ceftaroline-based combination therapy for methicillin-resistant Staphylococcus aureus bacteremia

PurposeMonotherapy with vancomycin or daptomycin remains guideline-based care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. Limited data support potential benefit of combination therapy with ceftaroline as initial therapy. We present an assessment of outcomes of patients initiated on early combination therapy for MRSA-B.MethodsThis was a single-center, retrospective study of adult patients admitted with MRSA-B between July 1, 2017 and April 31, 2023. During this period, there was a change in institutional practice from routine administration of monotherapy to initial combination therapy for most patients with MRSA-B. Combination therapy included vancomycin or daptomycin plus ceftaroline within 72 h of index blood culture and monotherapy was vancomycin or daptomycin alone. The primary outcome was a composite of persistent bacteremia, 30-day all-cause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were assessed. All outcomes were assessed using propensity score-weighted logistic regression.ResultsOf 213 patients included, 118 received monotherapy (115 vancomycin, 3 daptomycin) and 95 received combination therapy with ceftaroline (76 vancomycin, 19 daptomycin). The mean time from MRSA-positive molecular diagnostic blood culture result to combination therapy was 12.1 h. There was no difference between groups for the primary composite outcome (OR 1.58, 95% CI 0.60, 4.18). Time to microbiological cure was longer with combination therapy (mean difference 1.50 days, 95% CI 0.60, 2.41). Adverse event rates were similar in both groups.ConclusionsEarly initiation of ceftaroline-based combination therapy did not improve outcomes for patients with MRSA-B in comparison to monotherapy therapy.

Clinical, histopathological and parasitological follow-up of dogs naturally infected by Leishmania infantum before and after miltefosine treatment and associated therapies.

In Brazil, Visceral Leishmaniases is caused by Leishmania infantum, and domestic dogs are the main reservoirs in its urban transmission cycle. As an alternative to euthanizing dogs, miltefosine has been used to treat canine visceral leishmaniasis since 2016. In this study, we have assessed the efficacy of miltefosine for treating canine visceral leishmaniasis in a new endemic area through follow-up of naturally infected dogs was evaluated. The clinical, parasitological, and histopathological characteristics of 21 dogs naturally infected with L. infantum were assessed at three time points: on the day before initiating miltefosine treatment (T0), immediately after treatment completion (T1), and 6 months after treatment completion (T2). Three dogs were treated exclusively with miltefosine, while eighteen received combination therapy with miltefosine with other treatments such as allopurinol, domperidone and immunotherapy. Skin biopsies were obtained from the abdomen to assess inflammatory responses and to quantify parasite loads using qPCR. The parasites were isolated using aspirates acquired from popliteal lymph nodes. Molecular and parasitological analyses confirmed the presence of L. infantum in all dogs, validating the effectiveness of skin and lymph node samples for diagnosis. The clinical conditions of the infected animals were improved and the skin parasite load decreased after treatment, even when distinct combination therapies were performed. The histopathological assessment revealed a miltefosine-induced reduction in the inflammatory response and a decrease in amastigotes number. Furthermore, a positive correlation was established between the reduction in parasite load and the enhancement of clinical scoring, as well as a reduction in the skin inflammatory response. Our findings suggest that miltefosine-based combination therapies reduce skin parasite load and improve clinical outcomes, while the dogs treated with miltefosine alone showed increased parasitic load and worsened clinical staging at T2. Considering this data belonging to a recent transmission area, treatment strategy suggests effective in controlling canine visceral leishmaniasis.

Short-term renal and patient outcomes of primary immunoglobulin-associated mesangiocapillary glomerulonephritis: Insights from a developing country.

Primary immunoglobulin (Ig)-associated mesangiocapillary glomerulonephritis (Ig-MCGN) is an immune complex glomerulonephritis of unknown etiology. It is a common cause of chronic kidney disease in developing countries. There is limited data available on renal and patient outcomes of this disease from developing countries. To determine the short-term renal and patient outcomes of adults with a tissue-confirmed diagnosis of primary Ig-MCGN at a single center in Pakistan. A retrospective cohort study of adult patients was conducted on biopsy-proven Ig-MCGN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Secondary causes were excluded. The primary endpoint was renal survival without end-stage kidney disease (ESKD) or mortality. The secondary endpoint was the rate of remission during the 2-year follow-up period. Survival curves were made with the use of Kaplan-Meier estimates. A total of 163 patients were included in the study and their mean follow-up duration was 29.45 months ± 21.28 months. Among baseline characteristics, young age, lower estimated glomerular filtration rate, requirement of kidney replacement therapy, presence of crescents, and severity of interstitial fibrosis and tubular atrophy were found to have a significant association with renal outcomes. The renal outcomes were negatively correlated with the presence of hypertension, level of complements, and degree of proteinuria. In all, 63 (37.4%) patients were treated with steroids and 21 (13%) received combination therapy (cyclophosphamide with steroids). At 2 years, 124 (76.07%) patients were in complete remission or partial remission [56 (34.3%) and 68 (41.71%), respectively], while 32 (19.63%) patients progressed to ESKD and 7 (4.29%) patients died. The outcomes of primary Ig-MCGN are guarded in Pakistan and require further prospective studies to improve our understanding of this relatively common disease so that more personalized treatment approaches can be developed.

Clinical characteristics and prognostic analysis of diffuse large B-cell lymphoma with TP53 mutation

Exploring the clinical and pathological characteristics and prognostic factors of diffuse large B-cell lymphoma (DLBCL) patients with TP53 mutation. Data of 86 DLBCL patients with TP53 mutation treated with R-CHOP and 19 DLBCL patients with TP53 mutation treated with R-CHOP like regimen as first-line treatment at the Cancer Hospital of Chinese Academy of Medical Sciences (CAMS) and the Cancer Hospital of the CAMS in Shenzhen, China, from January 2006 to June 2023 were retrospectively analyzed. Multivariate Cox analysis was applied to assess the effects of the factors on survival. Among the 105 DLBCL patients with TP53 mutation, 56 were male (53.3%); the median age was 59 years. There were 54 cases with stage Ⅰ-Ⅱ and 51 cases with stage Ⅲ-Ⅳ diseases. The proportion of B-cell lymphoma 2 (BCL2) gene amplification was 9.5% (10/105). The complete response rate in the whole group of patients treated with the R-CHOP regimen was 28.6% (30/105). The median progression-free survival (PFS) was 10.1 (95%CI: 7.3-13.0) months, and the median overall survival (OS) was not reached. Stage Ⅲ-Ⅳ was a risk factor for OS (HR=2.80, 95%CI: 1.04-7.54), and elevated lactic dehydrogenase (LDH) was a risk factor for PFS (HR=2.86, 95%CI: 1.56-5.26) and OS (HR=2.90, 95%CI: 1.08-7.69). The median PFS was lower in patients with BCL2 amplification than in patients without amplification [4.0 (95%CI: 2.7-5.3) vs 11.3 (95%CI: 8.5-14.1) months, P=0.011]. Thirty-one of the 54 (57.4%) patients with stage Ⅰ-Ⅱ disease received combination therapy based on the R-CHOP protocol. In conclusion, stage Ⅲ-Ⅳ and elevated LDH were associated with poor prognosis in TP53 mutation DLBCL patients, and patients with BCL2 amplification had a poor prognosis. For TP53 mutation DLBCL patients with stage Ⅰ-Ⅱ disease, combination of therapeutic modalities based on the R-CHOP may improve the prognosis.

Positive impact of DPP-4 or SGLT2 inhibitors on mild cognitive impairment in type 2 diabetes patients on metformin therapy: A metabolomic mechanistic insight.

Mild cognitive impairment is increasingly recognized as a complication of type 2 diabetes (T2D). Although currently no disease-modifying treatments for cognitive disorders exist, interest surged in potential neuroprotective effects of newer anti-diabetic drugs. This study investigates the impact of newer anti-diabetic drug classes, dipeptidyl peptidase-4 (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) - on cognitive decline in T2D patients on metformin therapy. A prospective observational cohort study was conducted, with a follow-up duration of 6 months. The study compared the cognitive performance of T2D patients on metformin monotherapy to those on a combination of metformin with DPP-4i or SGLT2i, using the Montreal Cognitive Assessment Battery. A group of healthy volunteers served as a reference. At baseline, patients receiving combination therapy had a cognitive performance comparable to that of healthy volunteers, while those on metformin monotherapy scored lower. These differences persisted for patients who completed the follow-up, though there was no change within group. Baseline differences were independent of glycemic control, blood lipids, renal function, and serum inflammatory markers. Comprehensive metabolomics and lipidomics revealed that T2D patients on metformin monotherapy exhibited enriched purine, glutathione and sphingolipid metabolism, with alterations in xanthine, L-pyroglutamic acid, and several sphingomyelins. These changes suggest increased oxidative stress in T2D, mitigated in the combination therapy group, as evidenced by total serum antioxidant capacity. As such, we conclude that the combination of DPP-4i or SGLT2i with metformin positively impacts cognitive function in T2D patients by modulating metabolic pathways rather than improving glycemic control, peripheral diabetic complications, or systemic inflammation.

Efficiency of combination therapy versus monotherapy for the treatment of infections due to carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis

BackgroundFor resistant Gram-positive bacteria, evidence suggests that combination therapy is more effective. However, for resistant Gram-negative bacteria, no consensus has been reached. This study aims to comprehensively summarize the evidence and evaluate the impact of combination versus monotherapy on infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB).MethodsA systematic search was conducted in PubMed, Cochrane library, Web of Science, and Embase up to June 15, 2024, to identify relevant studies. This study included comparisons of monotherapy and combination therapy for treating infections caused by CRGNB. Topical antibiotics (i.e., inhalational or intratracheal administration) and monotherapy with sulbactam/relebactam was excluded. The primary outcome was mortality, and the secondary outcomes were clinical success and microbiological eradication. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated in order to systematically assess effect of treatment on mortality, clinical success and microbiological eradication. Subgroup analyses, publication bias tests, and sensitivity analyses were also performed.ResultsA total of 62 studies, including 8342 participants, were analyzed, comprising 7 randomized controlled trials and 55 non-randomized studies. Monotherapy was associated with higher mortality (OR = 1.29, 95%CI: 1.11–1.51), lower clinical success (OR = 0.74, 95%CI: 0.56–0.98), and lower microbiological eradication (OR = 0.71, 95%CI: 0.55–0.91) compared to combination therapy for CRGNB infections. Specifically, patients with carbapenem-resistant Enterobacteriaceae (CRE) infections receiving monotherapy had higher mortality (OR = 1.50, 95%CI: 1.15–1.95), comparable clinical success (OR = 0.57,95%CI: 0.28–1.16), and lower microbiological eradication (OR = 0.48,95%CI:0.25–0.91) than those receiving combination therapy. For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, no significant differences were observed in mortality (OR = 1.15.95%CI: 0.90–1.47), clinical success (OR = 0.95,95%CI: 0.74–1.24) and microbiological eradication (OR = 0.78,95%CI: 0.54–1.12).ConclusionsMonotherapy or combination therapy is controversial. The systematic review and meta-analysis suggested that monotherapy is associated with higher mortality, lower clinical success, and lower microbiological eradication for treating infection caused by CRGNB. The available evidence suggests that treatment should be selected based on the specific bacteria and antibiotic used. Monotherapy for CRE infections may lead to adverse outcomes. For CRAB infections, no significant differences were found between combination therapy and monotherapy.Systematic review registrationPROSPERO CRD42022331861.

Is nivolumab alone or in combination with ipilimumab more effective for treating lung cancer? a meta-analysis.

Nivolumab and ipilimumab combination immunotherapy has become a standard treatment option for certain cancers. However, the benefits of combination therapy compared to nivolumab monotherapy in lung cancer patients are not entirely clear. We aimed to evaluate whether nivolumab plus ipilimumab improves clinical outcomes in lung cancer patients compared to nivolumab monotherapy. A literature search was performed on PubMed, Web of Science, and Scopus from inception until November 2024 to identify relevant randomized controlled trials. The Cochrane risk of bias tool was used to assess the risk of bias, the hazard ratio (HR) was calculated for survival, risk ratios (RRs) were calculated for response rate and safety outcomes, and a random effects model meta-analysis was performed to estimate the safety and efficacy of the treatments. Seven trials comprising 2134 patients were included. Compared with patients receiving nivolumab monotherapy, non-small cell lung cancer patients who received combination therapy had better progression-free survival (HR = 0.82, 95% CI 0.71; 0.93, P < 0.01, low certainty), and there were no significant differences in overall survival (HR = 0.95, 95% CI 0.86; 1.0, P = 0.31, moderate certainty), or objective response rate (RR = 1.36, 95% CI 0.91; 2.02, P = 0.14 very low certainty). The combination group had a significantly greater risk of grade 3-4 adverse events (RR = 2.77, 95% CI 1.38; 5.56, P < 0.01, low certainty). Although combination treatment significantly improved progression-free survival in NSCLC patients, it was also associated with a greater risk of adverse events and treatment-related mortality than nivolumab monotherapy. The current evidence is insufficient for choosing combination treatment over nivolumab monotherapy.

Prescription Pattern of Antihypertensive Drugs in Chronic Kidney Disease Patients Attending - A Tertiary Care Hospital

Background: Chronic kidney disease exists both as a common cause of hypertension and complication of uncontrolled hypertension. This complex interplay of hypertension and CKD further increases the risk of adverse cardiovascular and cerebrovascular outcomes. Blood pressure control is pertinent in all stages of chronic kidney disease. Method: An observational descriptive cross-sectional study was conducted in Nephrology Department of Dhaka Medical College Hospital from January 2022 to December 2022. Total 264 hypertensive CKD patients were included in this study according to selection criteria. Collected data were processed and analyzed by using SPSS 26.0. p value of &lt; 0.05 was taken as statistically significant. Result: Among 264 CKD patients 58% male, 42% female and mean age was 49.43±13.87years. Only 67% patient achieved control of BP with antihypertensive. 53.8% patient were in stage-5 and 18.2% in stage-4 CKD. 85.6% patient received combination therapy. Among them 58.3% patients received two drug combination therapy. CCBs was prescribed in 169 patients. Amlodipine was 41.42% the preferred CCB and the combination of ARBs+CCBs was (28.7%) the frequently prescribed. Control of blood pressure was achieved in CKD patients taking monotherapy (p = 0.039) and on three drug combination therapy (p = 0.006). Conclusion: Calcium channel blocker is the treatment of choice in CKD patients with hypertension and commonly prescribed CCB is amlodipine. Combination of antihypertensive therapy is a better choice for control of hypertension. J Com Med Col Teachers Asso July 2024; 28(2): 70-74

Contraceptives or Hormone Replacement Therapy and Associations with Autoimmune Conditions: Exploring Effects of Estrogen Analog Supplementation.

The aim of this study was to investigate the impact of estrogen and progesterone analog supplementation on the development of autoimmune conditions. This retrospective observational study used data from the TriNetX network, which comprised over 100 million patients from 89 health care organizations. We compared patients exposed to estrogen and progesterone analogs to those exposed to progesterone-only therapy, using 1:1 propensity score matching based on age, ethnicity, and additional criteria. The primary outcomes were incidences of various autoimmune conditions. We included 3,338,925 patients in the group who received estrogen and progesterone and 2,090,758 patients in the group who received progesterone only. Prematching, the group who received combined therapy showed increased risks for Sjögren disease (risk ratio [RR] 1.46), rheumatoid arthritis (RR 1.1), and other autoimmune conditions. Postmatching, significant associations persisted for most conditions, with increased risks for systemic sclerosis, systemic lupus erythematosus, giant cell arteritis, Behcet disease, psoriatic arthritis, reactive arthritis, and ankylosing spondylitis. The group who received combination therapy appeared to have lower risks of developing antiphospholipid syndrome (RR 0.7). Combined estrogen and progesterone therapy is associated with an increased risk of several autoimmune conditions. The role of estrogen, despite its protective effects against some conditions, underscores the complex interplay of sex hormones in autoimmunity. Further prospective studies are needed to elucidate underlying mechanisms and evaluate causality.

Comparison of subcutaneous and intravenous infliximab in patients with inflammatory bowel disease showed no differences in immunogenicity or treatment persistence at 1 year

BackgroundInfliximab (IFX) effectiveness in inflammatory bowel disease (IBD) can be impaired by antidrug antibodies (ADA). Subcutaneous IFX has a different pharmacokinetic profile compared with intravenous administration, potentially affecting immunogenicity.MethodsRetrospective audit...

Combining moderate dosage of Bevacizumab with TAS-102 provides longer progression-free time in refractory metastatic colorectal Cancer

PurposeWe aimed to evaluate the efficacy of moderate doses of bevacizumab in combination with TAS-102 for the treatment of refractory metastatic colorectal cancer.MethodsA total of 261 patients with refractory mCRC were enrolled and categorized into two groups: TAS-102 combined with bevacizumab and TAS-102 alone. Patients in the bevacizumab combination group were divided into two subgroups based on a median dose of 3.3 mg/kg. Categorical variables were compared using the chi-square or Fisher’s exact test, and continuous variables were assessed using the t-test. The Cox proportional hazards model was used to adjust covariates. Survival analysis was performed using the log-rank test and Kaplan–Meier curves. Specific survival was evaluated using restricted mean survival time (RMST) and landmark analysis.ResultThe median progression-free survival (PFS) was 3.7 months in the TAS-102 combined with the bevacizumab group and 2.2 months in the non-bevacizumab group, showing significance in favor of the bevacizumab combination. Median overall survival (OS) was 9.4 months in the bevacizumab combination group and 10.3 months in the group that did not receive combination therapy. A survival benefit was observed within 9.5 months in both the RMST and landmark analyses. The PFS benefit was consistent across different doses of bevacizumab, while no significant difference in OS was observed compared to TAS-102 monotherapy. Both PFS and OS did not significantly differ between the different doses of bevacizumab.ConclusionModerate doses of bevacizumab and TAS-102 provided satisfactory efficacy over the standard dose within a limited timeframe of 9.5 months.

Capabilities of positron emission tomography/computed tomography in a comparative assessment of the effect of various targeted therapy options in patients with &lt;i&gt;EGFR&lt;/i&gt;-mutated non-small-cell lung cancer

BACKGROUND: No publications in the Russian medical literature have examined the potential of positron emission tomography combined with computed tomography through a comparative evaluation of the effect of various targeted therapies involving tyrosine kinase inhibitors in patients with non-small cell lung cancer and mutations in the EGFR gene. AIM: To explore the capabilities of positron emission tomography combined with computed tomography based on the RECIST 1.1 criteria and changes in SUVmax and SUVmean metabolic parameters for the comparative assessment of the tumor response to targeted monotherapy and combination therapy with tyrosine kinase inhibitors in patients with EGFR-mutant non-small cell lung cancer. MATERIALS AND METHODS: The 2019–2022 examination records of positron emission tomography combined with computed tomography with 18F-fluorodeoxyglucose (18F-FDG) in 105 patients with non-small cell lung cancer were analyzed, including 75 patients with EGFR-activating mutation. The radiation exposure was adjusted individually and ranged from 45 to 90 mSv. The volume activity of the 18F-FDG radiopharmaceutical was 260–500 MBq. The change in the total largest diameters of the target lesions and SUVmax and SUVmean metabolic parameters were assessed before treatment initiation and 1.5–2.0 months after it. The follow-up duration for the changes in positron emission tomography combined with computed tomography findings in 17 patients with non-small cell lung cancer was at least 12 months. RESULTS: According to positron emission tomography combined with computed tomography images and SUVmax and SUVmean changes, disease progression was significantly less common (p = 0.043 and p =0.029) in patients with EGFR-mutant non-small cell lung cancer from Groups 2 and 3 who received combination therapy with tyrosine kinase inhibitors and bevacizumab or chemotherapy than in Group 1 and control group (4.2% vs. 20.0%–21.8%). An insignificant trend (p =0.092) to a higher partial response to therapy (58.3% vs. 40.0%) was noted. Similar changes in the total largest diameters of the target lesions at the early stage of therapy appeared to be not significant (p =0.187). Within the long-term follow-up of some patients with non-small cell lung cancer, in at least 50% of cases, changes in the total largest lesion diameters are consistent with the relevant SUVmax and SUVmean alterations found in the first control study. CONCLUSIONS: Based on the positron emission tomography combined with computed tomography data and alterations in SUVmax and SUVmean metabolic parameters, the early tumor response to combined therapy with tyrosine kinase inhibitors and bevacizumab or chemotherapy compared with targeted monotherapy with tyrosine kinase inhibitors or chemotherapy of the control group was characterized by a significantly lower rate of metabolic disease progression, although a similar tendency of the change in the total largest diameters of target lesions according to RECIST 1.1. was not significant. Changes in SUVmax and SUVmean metabolic parameters at the early stage of therapy are at least 50% faster than similar changes in the total largest diameters of the target lesions, which can be used for the timely identification of patients with a high risk of further progression as determined by RECIST 1.1.

Efficacy of Combined Therapy With Silodosin and Solifenacin in Females With Overactive Bladder.

We aimed to assess the clinical efficacy and safety of combining silodosin and solifenacin for overactive bladder (OAB) in females. A retrospective analysis of 586 females with OAB was conducted. Patients received either combination therapy (silodosin 8 mg + solifenacin 5 mg) or monotherapy (solifenacin 5 mg) for 12 weeks. Baseline and follow-up assessments included the overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), voided volume (VV), and postvoid residual urine volume (PVR). Overall, 287 and 299 patients received combination therapy and monotherapy respectively. Both groups experienced significant improvements in OABSS and total IPSS after 12 weeks. The combination therapy group demonstrated a greater improvement in QoL compared to the monotherapy group (P=0.031). No significant differences were observed in Qmax or VV between the groups. However, the combination therapy group showed a significant reduction in PVR compared to the monotherapy group (P<0.001). Combining silodosin with solifenacin significantly improved OAB symptoms and QoL in females. This combination therapy was particularly effective in reducing postvoid residual volume compared to solifenacin alone. These findings suggest that adding an alpha-blocker to antimuscarinic therapy can enhance OAB management and patient satisfaction.

Assessment of novel biomarkers of renal dysfunction associated with lower urinary tract symptoms in men with benign prostatic hyperplasia

Introduction. The problem of diagnostics and treatment of patients with complex lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) remains highly relevant. Clinical diagnostic methods do not always allow timely prediction of changes in renal, upper and lower urinary tract function with different types of treatment intervention. The search for potential biomarkers allowing minimally invasive assessment of the bladder and renal function condition seems to be a promising direction of scientific research.Objective. To identify potential urine and serum biomarkers allowing to assess renal function in patients with LUTS/BPH.Materials &amp; methods. The study included 69 patients with LUTS/BPH and subsequently divided them into two groups. Group 1 included 48 patients with moderate LUTS who received combination therapy with alpha-1 adrenergic blockers (AABs) and 5-alpha reductase inhibitors (5ARIs). Group 2 included 21 patients with severe LUTS/BPH. Patients of group 2 underwent surgical treatment: transurethral resection of the prostate. In addition to standard research methods (IPSS, voiding diaries, laboratory, urodynamic and radiation techniques), to search for potential biomarkers in serum and urine, concentrations of: insulin-like growth factor binding protein-7 (IGFBP7), B-Cross Laps, Cystatin C, OPN, trefoil factor (TFF3), uromodulin, Clusterin, lactate dehydrogenase (LDH). The follow-up period for patients was 12 months.Results. The study noted that IGFBP7, Cystatin C, TFF3 in the blood serum, as well as LDH, Clusterin in the urine are associated with the severity of LUTS/BPH. Serum biomarker levels were initially higher in patients with severe LUTS compared to patients with moderate LUTS (group 1). The levels of these substrates decreased in patients of all groups during treatment (conservative therapy, surgical interventions for BPH). When assessing urinary biomarkers, the greatest decrease in Clusterin level by the end of follow-up was registered in group 1 patients, the least pronounced in group 2 patients. The initial value of LDH was twice higher in group 2 vs group 1 and progressively decreased after surgical treatment of bladder outlet obstruction.Conclusion. Biomarkers used to assess renal dysfunction in the development of LUTS/BPH are a promising area of scientific research. Panels of new markers will enable to predict renal dysfunction in patients with moderate-to-severe LUTS, which will improve the quality of medical care for this category of patients.

Multiparametric MRI-based Machine Learning Radiomics for Predicting Treatment Response to Transarterial Chemoembolization Combined with Targeted and Immunotherapy in Unresectable Hepatocellular Carcinoma: A Multicenter Study

Rationale and ObjectivesTo develop and validate multiple machine learning predictive models incorporating clinical features and pretreatment multiparametric magnetic resonance imaging (MRI) radiomic features for predicting treatment response to transarterial chemoembolization combined with molecular targeted therapy plus immunotherapy in unresectable hepatocellular carcinoma (HCC). Materials and methodsThis retrospective study involved 276 patients with unresectable HCC who received combination therapy from 4 medical centers. Patients were divided into one training cohort and two independent external validation cohorts. 16 radiomic features from six multiparametric MRI sequences and 2 clinical features were used to build six machine learning models. The models were evaluated using the area under the curve (AUC), decision curve analysis, and incremental predictive value. ResultsAlpha-fetoprotein and neutrophil-to-lymphocyte ratio are clinical independent predictors of treatment response. In the training cohort and two external validation cohorts, the AUCs and 95% confidence intervals for predicting treatment response were respectively 0.782 (0.673–0.793), 0.695 (0.514–0.708), and 0.679 (0.526–0.719) for the clinical model; 0.942 (0.846–0.932), 0.869 (0.700–0.881), and 0.868 (0.730–0.885) for the radiomics model; and 0.956 (0.859–0.942), 0.895 (0.738–0.903), and 0.892 (0.667–0.828) for the combined clinical-radiomics model. In the three cohorts, the incremental predictive value of the radiomics model over the clinical model was 49.2% (P < 0.001), 28.8% (P < 0.001), and 31.5% (P < 0.001). ConclusionThe combined clinical-radiomics model may provide a reliable and non-invasive tool to predict individual treatment responses and guide and improve clinical decision-making in combination therapy of HCC patients.

Safety and efficacy of generic nab-paclitaxel-based therapy in Chinese patients with malignant tumors in a real-world setting: a multicenter prospective observational study

ObjectiveThis study aimed to assess the safety and efficacy of generic nab-paclitaxel in the Chinese population in a real-world setting.MethodsThis prospective, multicenter, observational study enrolled patients with malignancies who received any generic nab-paclitaxel-based regimens in China. The primary endpoint was safety, and secondary endpoint was objective response rate (ORR). Logistic regression was used to explore risk factors for adverse events (AEs) of special interest (AESIs).ResultsBetween September 2019 and April 2023, 1168 patients were enrolled and evaluated for safety, and 602 were assessed for tumor response. Of 1168 patients, 169 (14.5%) received generic nab-paclitaxel monotherapy, and 999 (85.5%) received generic nab-paclitaxel-based combination therapy. Grade 3–4 AEs occurred in 19.3% (225/1168) patients, most commonly including neutrophil count decreased (7.6%), anemia (5.8%), and white blood cell decreased (5.7%). In subgroup analysis, peripheral sensory neuropathy was observed frequently in breast cancer (45.6%). Multivariate analysis showed that patients receiving combination therapy and ≥ 4 treatment cycles (OR, 1.925; 95% CI 1.363–2.719; p < 0.001) were more susceptible to the AESIs.ConclusionsThis study demonstrates a promising safety and efficacy of generic nab-paclitaxel-based regimens for Chinese patients with malignancies in a real-world setting, providing valuable insights for clinical decision-making.Clinical Trials.gov NCT04060290

Effectiveness of Fractional CO2 Laser and Topical Centella asiatica Combination Therapy in Striae Distensae (Stretch Marks).

Introduction: Striae distensae (SD) are a skin disorder characterized by linear atrophic depression of the dermis due to stretching of the skin. There are various SD therapy modalities, namely topical therapy, peeling, microneedling, platelet-rich plasma, and laser. Until now, there has been no standard therapy for SD, but several therapeutic modalities can reduce clinical symptoms, so knowledge about the current management of SD is needed. Methods: The research method used an experimental research design with consecutive sampling technique in SD patients at the Dermatology, Venereology and Aesthetics clinic of Mohammad Hoesin Hospital, Palembang, during the research period. This study aimed to determine the effectiveness of combination therapy with fractional CO2 laser and Centella asiatica in SD. Results: This study included 22 SD patients who met the inclusion criteria and received combination therapy with fractional CO2 laser and Centella asiatica. The results of the analysis of differences in the Index of Striae Distensae Assessment (INA) score, Dermatology Life Quality Index (DLQI) score and VAS score revealed that there was a significant difference in the mean decrease in the INA score between the baseline and week 12 (P=0.014), as well as in the DLQI score between the baseline and week 12 (P=0.000). There was a significant difference in the mean VAS score between the baseline and week 4 (P=0.000). Conclusion: These findings indicate that the combination of fractional CO2 laser and topical Centella asiatica effectively reduces the severity of SD, improves patients' quality of life, and decreases associated pain. Further studies could explore long-term effects and optimize treatment protocols for even better outcomes.

Cytokine release syndrome caused by immune checkpoint inhibitors: a case report and literature review.

Immune checkpoint inhibitors (ICIs) have gained widespread application in the treatment of malignant tumors. Cytokine release syndrome (CRS) is a systemic inflammatory response triggered by various factors, including infections and immunotherapy. We present a case of CRS occurring in a gastric cancer patient after receiving combination therapy of tislelizumab, anlotinib and combination of capecitabine and oxaliplatin. Nineteen days after the third dose of tislelizumab, the patient experienced sudden unconsciousness, frothing at the mouth, convulsions and other clinical manifestations resembling epileptiform seizures. Elevated inflammatory markers, cytokine levels and ferritin were markedly increased. Given the absence of definite clinical evidence for metastasis and infection, the diagnosis of CRS was considered. Subsequent management with glucocorticoids and intravenous immunoglobulin resulted in the patient's improvement. However, antitumor therapy was halted, ultimately leading to death. The administration of ICIs can incite CRS, a severe, rapidly progressing condition with a poor prognosis, demanding clinical attention. Cytokines play a dual role in the pathophysiology of immune-related adverse events by mediating self-tolerance attenuation and enhancing the activation of cytotoxic T cells in the antitumor process of ICIs. The therapy of glucocorticoids combined with cytokine inhibitors may become an effective remedy.

One or two? Comparison of the cardiorenal effects between combination therapy and monotherapy with SGLT2i or GLP1RA.

This study aimed to evaluate the cardiorenal effect of combining sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) when compared with monotherapy of either agent in patients with type 2 diabetes (T2D). PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov were systematically searched from inception to June 2024. Eligible studies included randomised controlled trials and observational studies assessing that compared with SGLT2i or GLP-1RA monotherapy, the risk of cardiorenal outcomes in patients with T2D who treated with combination therapy. Pooled relative risk (RR) and 95% confidence intervals (CIs) were computed in random-effects model. In all, five RCTs, 10 post hoc analyses and one observational study were included. The reduced risk of the composite cardiovascular outcome was observed in patients receiving combination therapy of SGLT2i and GLP-1RA when compared with SGLT2i monotherapy (RR = 0.57, 95% CI 0.38-0.86, p = 0.008) or GLP-1RA monotherapy (RR = 0.77, 95% CI 0.65-0.91, p = 0.002). Likewise, the composite renal adverse events were less frequent in patients receiving combination therapy of SGLT2i and GLP-1RA when compared with SGLT2i monotherapy (RR = 0.69, 95% CI 0.59-0.82, p < 0.001) or GLP-1RA monotherapy (RR = 0.66, 95% CI 0.53-0.83, p < 0.001). Compared with GLP-1RA monotherapy, the combination therapy of SGLT2i and GLP-1RA was associated with lower risks of heart failure-related outcomes (RR = 0.63, 95% CI 0.51-0.77, p < 0.001) and all-cause mortality (RR = 0.66, 95% CI 0.50-0.88, p = 0.004) in patients with T2D. The cardiorenal benefits might be magnified with the combination therapy of SGLT2i and GLP-1RA when compared with monotherapy of either agent. Further investigations are needed to validate the findings.