Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.

BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.

Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.

Background and Aim: Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates. Methods: A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3 months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P = 0.0008) and 3.07 (95% CI: 1.81-5.20, P < 0.0001), respectively. However, the survival advantage disappeared after 6 months (OR: 2.96, 95% CI: 0.99-8.85, P = 0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P = 0.41). Conclusion: This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12 months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit.

Efficacy of pentoxifylline for the treatment of bipolar I/II patients with treatment-resistant depression: A proof-of-concept, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Immune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies. OBJECTIVE: To evaluate the anti-depressant effects of the anti-inflammatory drug, pentoxifylline (PTX) in TRD bipolar I/II adult subjects. METHODS: This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at Hawler Psychiatric Hospital and Private Clinic in Erbil, Iraq. Participants were confirmed as being qualified for bipolar I/II depression based on DSM-5 criteria. Data were analyzed using modified intent-to-treat analysis. RESULTS: There were no significant differences between the two groups in Hamilton Rating Scale for Depression-17 (HAM-D-17) scores (χ2=1.9, P =.48) or a significant time × treatment interaction (χ2=7.1, P=.54). Nevertheless, a significant effect of time was observed with both groups' reduction in HAM-D-17 scores from the start to the endpoint (χ2= 2.11, P=.002). Besides, a significant time × treatment × CRP interaction was found (χ2=3.1, P=0.016), where there was more reduction in HAM-D-17 score in PTX-treated subjects with CRP> 7.1 mg/L. The response rate difference between PTX and the placebo group did not reach a significance level (χ2=0.84, p=0.43). Furthermore, serum concentrations of TNF-α, CRP, and IL-6 significantly reduced at week 12 in the PTX group (P=.007,.04, and <.001, respectively). CONCLUSION: The current proof of concept study found that in terms of overall anti-depressant effectiveness in bipolar patients with TRD, PTX is not superior to placebo. However, it may improve depressive mood in a subpopulation of subjects with a higher pretreatment inflammatory profile.

Ginkgo biloba extract prescriptions are associated with less frequent repeat visits to ENT doctors due to tinnitus: a retrospective cohort study.

Objectives: We aimed to evaluate the drug utilization of Ginkgo biloba extract (Gbe), systemic corticosteroids (CSs), and pentoxifylline (PTXF) for the treatment of acute tinnitus by analyzing electronic patient health record data. In addition, we assessed whether the different drug treatments were associated with different frequencies of repeat visits to ear, nose, and throat (ENT) doctors. Methods: This retrospective cohort study used data from the IQVIA Disease Analyzer (DA) database. It included patients with an initial diagnosis of tinnitus between January 2005 and December 2021, treated by ENT specialists in Germany. Results: Of 111,629 patients meeting all selection criteria, 51,205 received prescriptions of Gbe, 34,817 of systemic CSs, and 25,607 of PTXF. Gbe prescription was associated with significantly lower odds of a repeat consultation due to tinnitus compared to systemic CSs [odds ratio (OR) 0.91; 95% confidence interval (CI): 0.88-0.95] as well as PTXF (OR 0.74; 95% CI: 0.72-0.77). This association was significant in both men and women and in some age groups. Conclusion: Gbe is the most frequently ENT specialist-prescribed drug for the treatment of acute tinnitus. It is associated with a reduced likelihood of patients consulting their ENT specialist for tinnitus again compared to systemic CSs and PTXF.

Negative Results, Positive Outcome: A Case of Primary Livedoid Vasculopathy With an Elusive Laboratory Workup.

Livedoid vasculopathy (LV) is a chronic, recurrent thrombotic vasculopathy characterized by painful ulcerations on the lower extremities, which heal slowly and leave atrophic white scars known as "atrophie blanche." This report presents the case of a 31-year-old woman with a 4-year history of recurrent painful ulcerations on her legs and feet. A skin biopsy revealed findings consistent with LV, and an exhaustive laboratory workup ruled out secondary causes such as thrombophilia, malignancies, autoimmune diseases, and peripheral arterial disease. The patient showed remarkable improvement with a treatment regimen of pentoxifylline, nifedipine, and warfarin, resulting in complete ulcer resolution and sustained remission over 5 months. Our case highlights the importance of a comprehensive diagnostic approach and a multidisciplinary treatment strategy in managing primary LV to achieve remission and prevent recurrence of skin ulcerations.

Association Between Pentoxifylline Use and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Multi-Institutional Cohort Study.

BACKGROUND: Pentoxifylline is administrated to improve the hemodynamics of patients with chronic kidney disease (CKD). Despite the improvement of capillary blood flow velocity in retina after pentoxifylline use, no evidence has been provided to prove the protective effect for diabetic retinopathy (DR). Therefore, this study aimed to assess the risk of DR in pentoxifylline users with CKD and diabetes mellitus (DM). MATERIAL AND METHODS: In this retrospective cohort study, Chang Gung Research Database, which includes the data of patients with CKD and DM from 2003 to 2019, was used. Each calendar year was divided into 4 data units with 3 months each for every patient and every year during the follow-up. The ocular outcomes were new-onset DR, DR-related complications, and vitreoretinal interventions. RESULTS: Total 56,439 patients without preexisting DR and 5,039 patients with preexisting DR were included in this study. Exposure to pentoxifylline was associated with elevated risk of new-onset DR (adjusted hazard ratio = 1.24, 95% confidence interval = 1.13-1.36) in patients without preexisting DR. Additionally, exposure to pentoxifylline was associated with elevated risk of DR-related complications and vitreoretinal interventions in patients with or without preexisting DR. CONCLUSIONS: Exposure to pentoxifylline is associated with elevated risk of DR, regardless of whether patients have preexisting DR.

Is the use of Pentoxifylline and Tocopherol effective in the treatment of Osteoradionecrosis of the jaws or for the treatment of medicationosteonecrosis of the jaw? An overview.

PURPOSE: The aim of the present study was to determine the methodological quality of systematic reviews that evaluated the effectiveness of pentoxifylline and tocopherol (PENTO) in the treatment of osteoradionecrosis of the jaw (ORNJ) and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Searches were performed in Databases including PubMed, Scopus, LILACS, DARE, Cochrane Library, and SIGLE through OpenGrey until March 2024, were evaluated by two independent reviewers to answer the following question: Is the use of PENTO protocol effective in the treatment of ORNJ or for the treatment of MRONJ? RESULTS: A total of 256 articles were initially identified; however, following the use of appropriate inclusion and exclusion criteria, five systematic reviews were identified for detailed analysis. The final study sample comprised 588 patients: 397 patients with ORN and 197 patients with MRONJ who were treated with PENTO. The total recovery of individuals who used the PENTO protocol was 62,2 % for ORN and 100 % for MRONJ, with a follow-up period of 1 month to 10 years. The methodological quality of the studies was assessed using the AMSTAR 2 tool, in which four were of low quality and 1 moderate quality. CONCLUSION: The treatment of ORN and MRONJ with pentoxifylline and tocopherol has shown good results in the studies presented, with a partial or total reduction in bone exposure. However, the low quality of the relevant reports highlights the need for primary and secondary studies with better methodological rigor to reduce bias and provide reassurance for this treatment option.

Activation of AMPK/mTOR-Driven Autophagy and Suppression of the HMGB1/TLR4 Pathway with Pentoxifylline Attenuates Doxorubicin-Induced Hepatic Injury in Rats.

Despite being an effective chemotherapeutic agent, the clinical use of doxorubicin (DOX) is limited by several organ toxicities including hepatic injury. Pentoxifylline (PTX) is a methylxanthine derivative with marked anti-inflammatory and anti-apoptotic features. It is unknown, however, whether PTX can mitigate DOX-evoked hepatotoxicity. This study aims to explore the potential hepatoprotective impact of PTX in DOX-induced hepatic injury and the underlying molecular mechanisms. Histopathology, immunohistochemistry, and ELISA were used to examine liver tissues. The current findings revealed that PTX administration to DOX-intoxicated rats mitigated the pathological manifestations of hepatic injury, reduced microscopical damage scores, and improved serum ALT and AST markers, revealing restored hepatic cellular integrity. These favorable effects were attributed to PTX's ability to mitigate inflammation by reducing hepatic IL-1ß and TNF-α levels and suppressing the pro-inflammatory HMGB1/TLR4/NF-κB axis. Moreover, PTX curtailed the hepatic apoptotic abnormalities by suppressing caspase 3 activity and lowering the Bax/Bcl-2 ratio. In tandem, PTX improved the defective autophagy events by lowering hepatic SQSTM-1/p62 accumulation and enhancing the AMPK/mTOR pathway, favoring autophagy and hepatic cell preservation. Together, for the first time, our findings demonstrate the ameliorative effect of PTX against DOX-evoked hepatotoxicity by dampening the hepatic HMGB1/TLR4/NF-κB pro-inflammatory axis and augmenting hepatic AMPK/mTOR-driven autophagy. Thus, PTX could be utilized as an adjunct agent with DOX regimens to mitigate DOX-induced hepatic injury.

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells.

Aim: Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. Methods: The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between CHI3L1 gene expression and NSCLC patients' survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Results: Pentoxifylline slightly decreased the expression levels of CHI3L1, ß-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. Conclusion: This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.

Tadalafil versus pentoxifylline in the management of diabetic kidney disease: a randomized clinical trial.

AIMS: To investigate the efficacy and safety of tadalafil (TAD) versus pentoxifylline (PTX) in the management of diabetic kidney disease (DKD). Some animal studies and clinical trials reported that tadalafil and pentoxifylline have a reducing effect on different blood glucose parameters and lipid profiles which contribute to progress the patients with diabetes mellitus (DM) to DKD. METHODS: From February 2022 to March 2023, 90 patients with type 2 DM and DKD (micro-albuminuria) were enrolled in this randomized-controlled study. The patients were randomized into three equal groups: control group, TAD group, and PTX group. The three groups received traditional blood glucose lowering therapy + ramipril 10 mg PO. The TAD group also received tadalafil 20 mg PO every other day. The PTX group also received pentoxifylline 400 mg PO twice daily. RESULTS: Both TAD and PTX groups produced statistically significant improvement in the primary outcomes by a significant reduction in Urinary albumin/creatinine ratio (UACR) which was pronounced by a reduction percentage of-47.47%, -53.73% respectively. In addition to a significant decrease in Hemoglobin A1C (HbA1c) (mmol/mol), Fasting blood glucose (FBG), 2-h postprandial blood glucose (2-h PPG) (p < 0.001). Only the PTX group showed a significant increase in Cr Cl and a significant decrease in S. Cr (p < 0.001). Only the TAD group showed a significant increase in high-density lipoprotein-cholesterol (HDL-C) (p < 0.001), while the PTX group showed a significant decrease in low-density lipoprotein-cholesterol (LDL-C) (p-value 0.011), and triglyceride (p-value 0.002). Both TAD and PTX groups showed a decrease in tumor necrosis factor-α (TNF-α) which was significant only in the PTX group (p < 0.001). There was a significant increase in malondialdehyde (MDA) (p < 0.001), and an increase in urinary neutrophil gelatinase-associated Lipocalin (uNGAL) (p-value 0.850, 0.014 respectively) which was significant only in the PTX group. CONCLUSIONS: The use of tadalafil or pentoxifylline may serve as an effective adjuvant therapy for patients with diabetic kidney disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05487755, July 25, 2022.

Reno-protective effect of nicorandil and pentoxifylline against potassium dichromate-induced acute renal injury via modulation p38MAPK/Nrf2/HO-1 and Notch1/TLR4/NF-κB signaling pathways.

BACKGROUND: Occupational and environmental exposure to chromium compounds such as potassium dichromate (PDC) (K2Cr2O7) has emerged as a potential aetiologic cause for renal disease through apoptotic, and inflammatory reactions. The known potent antioxidants such as nicorandil (NIC) and/or pentoxifylline (PTX) were studied for their possible nephroprotective effect in PDC-treated rats. METHODS: Forty male Wistar rats were divided into five groups; control, PDC group, NIC+PDC, PTX+PDC group, and combination+PDC group. Nephrotoxicity was evaluated histopathologically and biochemically. Invasive blood pressure, renal function parameters urea, creatinine, uric acid and albumin, glomerular filtration rate markers Cys-C, Kim-1 and NGAL, inflammatory markers IL-1ß, IL-6, TNF-α, TGF-ß, COX-II, p38MAPK, NF-κB and TLR4, oxidative stress SOD, GSH, MDA, MPO, HO-1 and Nrf2 and apoptotic mediators Notch1 and PCNA were evaluated. Besides, renal cortical histopathology was assayed as well. RESULTS: PDC led to a considerable increase in indicators for kidney injury, renal function parameters, invasive blood pressure, oxidative stress, and inflammatory markers. They were markedly reduced by coadministration of PDC with either/or NIC and PTX. The NIC and PTX combination regimen showed a more significant improvement than either medication used alone. Our results demonstrated the nephroprotective effect of NIC, PTX, and their combined regimen on PDC-induced kidney injury through suppression of oxidative stress, apoptosis, and inflammatory response. CONCLUSION: Renal recovery from PDC injury was achieved through enhanced MAPK/Nrf2/HO-1 and suppressed Notch1/TLR4/NF-κB signaling pathways. This study highlights the role of NIC and PTX as effective interventions to ameliorate nephrotoxicity in patients undergoing PDC toxicity.

Pregnancy and neonatal outcomes of ICSI using pentoxifylline to identify viable spermatozoa in patients with frozen-thawed testicular spermatozoa.

Introduction: Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases of absolute asthenozoospermia has been demonstrated for ICSI, data related to babies born from the PF-ICSI are still severely lacking. Concerns have been raised regarding the potential embryotoxicity of PF due to the controversial results obtained from the analysis of this compound on animal embryo development. This study aimed to determine whether the application of PF to trigger frozen-thawed TESA (testicular sperm aspiration) spermatozoa increases the risk of adverse obstetric and neonatal outcomes compared with non-PF frozen-thawed TESA ICSI and conventional ICSI using fresh ejaculation. Materials and methods: A total of 5438 patients were analyzed in this study, including 240 patients underwent PF-TESA ICSI (ICSI using PF triggered frozen-thawed testicular spermatozoa), 101 patients underwent non-PF TESA ICSI (ICSI using frozen-thawed testicular spermatozoa) and 5097 patients underwent conventional ICSI using fresh ejaculation. Propensity score matching was executed to control the various characteristics of patients. Results: No significant differences in pregnancy outcomes were observed among the three groups (PF-TESA ICSI, non-PF TESA ICSI and conventional ICSI), including biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live birth, following propensity score matching. Additionally, neonatal outcomes were found to be similar among the three groups, with no statistical differences observed in the birth defect, birth weight, gestational age, preterm birth, and early-neonatal death. Discussion and conclusion: PF-ICSI may be an alternative treatment in patients using frozen-thawed testicular spermatozoa, resulting in comparable pregnancy and neonatal outcomes.

Effect of pentoxifylline on endothelial dysfunction, oxidative stress and inflammatory markers in STEMI patients.

Aim: ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). Methods: 43 patients were randomized to pentoxifylline (PTX) 400 mg thrice daily (n = 22) or placebo (n = 21). Soluble vascular cell adhesion molecule-1, malondialdehyde, interleukin-1 (IL-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) were assessed at baseline and 2 months. Results: After 2 months, no significant difference was observed in markers' levels between the 2 groups. However, a within-group comparison revealed a statistically significant change in hs-CRP in the PTX group (10.057 (9.779-10.331) versus 9.721 (6.102-10.191)), p = 0.032. Conclusion: PTX for 2 months in STEMI patients was safe and well-tolerated but had no significant detectable effect on ED, oxidative stress or inflammatory markers. Clinical Trial Registration: NCT04367935 (ClinicalTrials.gov).

This study examined the effect and the safety of a drug called pentoxifylline in patients who have recently had a heart attack. Pentoxifylline can possibly reduce inflammation and is used for patients with blood flow issues. The study involved 43 participants, 22 receiving pentoxifylline and 21 receiving a placebo for 2 months. We measured different markers related to inflammation and heart health before and after. Overall, there was no significant difference between the groups, but patients who received pentoxifylline experienced less inflammation according to only one of the markers measured. This study concluded that the prescription of pentoxifylline after a heart attack is safe, well-tolerated and without notable side effects. Still, we recommend larger and longer studies to be sure of its effect.

Investigation of the effects of pentoxifylline and alpha tocopherol treatment on recovery in rats with Achilles tendon rupture.

Although the Achilles tendon is the largest and strongest tendon in the body, healing of the Achilles tendon is the most common injury, and this process is difficult due to poor tendon circulation; moreover, the underlying mechanism has not been fully elucidated. In our study, we aimed to investigate the effects of pentoxifylline and alpha-tocopherol administered separately or in combination on rats with Achilles tendon injury. Forty-eight male Wistar rats weighing 230 ± 30 g were used in the study. The rats were randomly divided into eight groups of six animals each. Tendons were evaluated histopathologically and biomechanically. According to the statistical analysis, the vascularity density in the pentoxifylline group on day 14 was significantly greater than that in the other groups (p < 0.05). The collagen arrangement in the pentoxifylline and alpha-tocopherol groups on day 14 was found to be firmer and smoother than that in the control group (p < 0.05). The collagen arrangement in the pentoxifylline group on day 28 was greater than that in the other groups (p < 0.05). The biomechanical results were significantly greater in all groups (p < 0.05). Pentoxifylline contributed to tendon healing both through neovascularization in the early period and by improving collagen orientation in the late period, while alpha-tocopherol had a positive effect on collagen orientation in the early period. No beneficial effects were observed when pentoxifylline and alpha-tocopherol were used together. We believe that further research is needed to understand the effects of this combination therapy on tendon healing.

Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.

Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.

Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ. METHODS: A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized. RESULTS: Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation. DISCUSSION: While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.

The potential for improved outcomes in the prevention and therapy of diabetic kidney disease through 'stacking' of drugs from different classes.

Aggressive therapy of diabetic kidney disease (DKD) can not only slow the progression of DKD to renal failure but, if utilized at an early enough stage of DKD, can also stabilize and/or reverse the decline in renal function. The currently recognized standard of therapy for DKD is blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). However, unless utilized at a very early stage, monotherapy with these drugs in DKD will only prevent or slow the progression of DKD and will neither stabilize nor reverse the progression of DKD to renal decompensation. Recently, the addition of a sodium-glucose cotransporter-2 inhibitor and/or a mineralocorticoid receptor blocker to ACE inhibitors or ARBs has been clearly shown to further decelerate the decline in renal function. The use of glucagon-like peptide-1 (GLP-1) agonists shown promise in decelerating the progression of DKD. Other drugs that may aid in the deceleration the progression of DKD are dipeptidyl peptidase-4 inhibitors, pentoxifylline, statins, and vasodilating beta blockers. Therefore, aggressive therapy with combinations of these drugs (stacking) should improve the preservation of renal function in DKD.