Topical phenytoin improves wound healing with analgesic and antibacterial properties and minimal side effects: a systematic review.

BACKGROUND: Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited. OBJECTIVE: To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types. MATERIALS AND METHODS: The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects. RESULTS: The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient. CONCLUSION: Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds. BACKGROUND: Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited. OBJECTIVE: To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types. MATERIALS AND METHODS: The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects. RESULTS: The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient. CONCLUSION: Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.

Efficacy of Sequential Therapy as the First-Line Treatment in the Eradication of Helicobacter pylori.

The Helicobacter pylori infection is a significant issue in global health as it is associated with a range of gastrointestinal disorders and an elevated likelihood of developing stomach cancer. The declining efficacy of standard triple therapy (TT) as the recommended treatment can be attributed to the emergence of drug-resistant strains. Sequential therapy (ST) has been recognized as an alternative approach, wherein a combination of proton-pump inhibitor (PPI) and amoxicillin is administered for the initial five days, followed by a combination of PPI, clarithromycin, and metronidazole for the subsequent five days. In this comprehensive systematic review and meta-analysis, we have thoroughly assessed the effectiveness and tolerability of ST as a primary treatment option in comparison to TT for the eradication of H. pylori. The analysis comprised a total of 15 randomized controlled trials, encompassing a sample size of 5,219 patients. The collective findings indicate that ST exhibits promise as it achieves higher rates of eradication. Additionally, it is worth noting that this approach has the potential to yield cost savings and enhance treatment compliance when compared to TT. To summarize, this systematic review and meta-analysis provide evidence that ST is a viable option for the initial treatment of H. pylori eradication. It shows potential benefits compared to the standard TT, especially when there is resistance to clarithromycin. In order to establish ST as the preferred first-line treatment, it is imperative that additional research be conducted to address the aforementioned limitations and thoroughly investigate its long-term efficacy and safety profiles. Nevertheless, it is required that additional research be conducted in order to adequately tackle the constraints of the current studies and solidify its position as a favored treatment alternative. It is also essential to consider ST as a viable approach to improve the rates of H. pylori eradication. This method should be thoroughly examined in clinical practice to gain a deeper understanding of its effectiveness.

Tenofovir-Induced Renal Dysfunction Among HIV-Infected Patients: A Systematic Review.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug widely used as part of antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV-1) infection. Negative effects of tenofovir include impaired kidney function, especially with long-term use. In studies conducted among HIV-positive individuals, we found evidence of extensive kidney damage associated with TDF use. Despite the therapeutic importance of this consequence, its continued use in ART regimens was not contraindicated. The therapeutic and long-term effects of TDF are a major concern. However, in countries or settings where resources are limited and renal function monitoring cannot be ensured, screening methods to detect ART-related renal failure are still supported by data. Therefore, it is safe to re-evaluate the use of TDF-based ART. However, adherence to guidelines may be hampered by insufficient laboratory testing in low- and middle-income countries. More research is also needed among people under 18 years of age and pregnant and breastfeeding mothers.

Fluid Resuscitation in Septic Patients.

Sepsis is a life-threatening organ failure caused by a dysregulated response to infection. Fluid resuscitation and vasopressors are used to maintain systolic blood pressure and organ perfusion. Fluid resuscitation can be done with liberal or restricted fluids as well as colloids or crystalloid fluids. This review analyses the evidence for the use of liberal or restrictive fluids and colloids or crystalloids for the management of sepsis. A methodical search was conducted across PubMed, Cochrane Library, and ScienceDirect, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines were followed for this study. Randomized controlled trials and retrospective observational studies were included in this study. Liberal and restrictive fluid strategies were found to be comparable in efficacy, but restrictive fluid regimens had the added benefit of a lower incidence of fluid overload. Balanced crystalloids were safer and more effective when compared to normal saline. Albumin replacement was found to be safe and showed efficacy in reducing mortality in patients with sepsis and septic shock.

Eculizumab Versus Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome: A Systematic Review.

Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. The complement cascade plays an integral role in aHUS. Mutations in the complement cascade, especially in the alternative pathway (AP) lead to an unregulated and continuous activation of the cascade. Eculizumab and ravulizumab are humanized monoclonal antibodies that inhibit the complement cascade. This systematic analysis reviews the evidence for both antibodies to compare them in terms of safety and efficacy. This review will also assess the evidence for biomarker associations with interventions, the role of genetic mutations in the prognosis of disease, and the financial burden of both treatment options. An in-depth search was conducted across PubMed, Science Direct, and Cochrane Library following the PRISMA 2020 guidelines. Both eculizumab and ravulizumab were comparable in safety and efficacy but ravulizumab was preferred by patients and their caregivers as it posed a lower financial burden and had less frequent dosing. Soluble complement 5b-9 (sC5b), especially in urine, has the potential to be used as a biomarker to assess response to treatment. Genetic mutations, especially mutations in complement factor I (CFI), membrane cofactor protein (MCP), and complement factor H (CFH), were associated with a higher risk of recurrence, and therefore care should be taken when attempting to discontinue treatment in this subset of patients. Treatment with a monoclonal antibody should be initiated as soon as a genetic mutation is identified. Blinded, double-arm, clinical trials preferably with larger sample sizes are needed to effectively compare both the monoclonal antibodies.

Comparative Safety and Efficacy of Immunosuppressive Regimens Post-kidney Transplant: A Systematic Review.

Immunosuppressive agents are used post-organ transplant to prevent acute rejection and graft losses. Tacrolimus, the most widely used immunosuppressive agent for kidney transplant recipients, has unfavorable side effects such as new-onset diabetes after transplant, nephrotoxicity, and electrolyte imbalances. Other drug groups such as the mammalian target of rapamycin (mTOR) inhibitors, belatacept, and bleselumab have been used to either substitute calcineurin inhibitors or reduce their exposure. This systematic analysis reviews evidence from randomized controlled trials to compare the safety and efficacy of various immunosuppressive regimens for kidney transplant recipients. An in-depth methodical search was conducted across PubMed, Cochrane Library, and Mendeley. PRISMA 2020 guidelines were followed for this study. Randomized controlled trials comparing varying regimens were included in this study. While there was no difference in safety and efficacy between once-daily and twice-daily tacrolimus, mTOR inhibitors showed to be a viable option for a reduced tacrolimus exposure regimen. Calcineurin inhibitor avoidance and early steroid withdrawal regimens both showed increased rates of rejection. Based on these findings, a regimen containing once-daily tacrolimus and an mTOR inhibitor with or without corticosteroid is a viable immunosuppressive regimen post-kidney transplant. Further trials, especially ones with longer follow-up periods, are needed to explore these regimens' long-term safety and efficacy.

Comparative Study of Safety and Efficacy of Angiotensin-Receptor Blockers and Anti Amyloid-ß Monoclonal Antibodies for the Treatment of Alzheimer's Disease: A Systematic Review.

Amyloid-ß (Aß) plaques and Neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) pathology. Recent advances to find a cure for AD have led to the exploration of Anti-Aß monoclonal antibodies and angiotensin-receptor blockers (ARBs). The antibodies can decrease plaque formation or remove already formed plaques. ARBs increase angiotensin II (AT2) levels and decrease the effect of AT2 on the AT1 receptor (AT1R). This systematic analysis reviews evidence of monoclonal antibodies (Aducanumab, Lecanemab, Donanemab, and Solanezumab) and ARBs in managing AD. An in-depth methodical search was conducted across PubMed, Science Direct, and Mendeley. PRISMA 2020 guidelines were followed for this study. Randomized control trials for antibodies and ARBs and one retrospective cohort study were included. The comparison was made among studies that shared similar measured outcomes. Antibodies were found to be more effective than ARBs, with Aducanumab and Lecanemab being the most effective. ARBs, on the other hand, were found to be the safer choice. Further trials of longer duration and larger sample sizes are needed to explore both groups' long-term safety and efficacy.

Outcomes and motives for not proceeding with the second stage bilateral knee replacement: a comparison of cancelled and completed bilateral total knee arthroplasty.

BACKGROUND: Staged bilateral total knee arthroplasty (TKA) is a common treatment option for patients with bilateral symptomatic knee osteoarthritis, yet some patients do not proceed with their second procedure. Our study aimed to identify the rate and reasons why patients did not proceed with their second procedure and compare their functional outcomes, satisfaction and complication rates with those of patients who had completed a staged bilateral TKA. METHODS: We determined the proportion of patients who underwent TKA but did not proceed with planned surgery for the second knee within 2 years, and compared their satisfaction with surgery, improvement in the Oxford Knee Score (OKS) and complications between groups. RESULTS: Our study included 268 patients: 220 patients who underwent staged bilateral TKA and 48 patients who cancelled their second procedure. The most common reason for not proceeding with the second procedure was a slow recovery after the first TKA (43.2%), followed by functional improvement in symptoms in the unoperated knee negating the need for surgery (27.3%), poor experience with the first surgery (22.7%), treatment of other comorbidities necessitating cancellation of their second procedure (4.6%) and employment reasons (2.3%). Patients who cancelled their second procedure were noted to have a worse postoperative OKS improvement (p < 0.001) and lower satisfaction rate (p < 0.001), than patients who underwent staged bilateral TKA. CONCLUSION: About one-fifth of patients scheduled for staged bilateral TKA declined to proceed with the second knee surgery within 2 years showing a substantially decreased functional outcome and satisfaction rate. However, more than one-quarter (27.3%) of patients noted improvements in their contralateral (unoperated) knee, such that a second surgery was no longer felt to be necessary.

Advances in genome editing: the technology of choice for precise and efficient ß-thalassemia treatment.

Beta (ß)-thalassemia is one of the most significant hemoglobinopathy worldwide. The high prevalence of the ß-thalassemia carriers aggravates the disease burden for patients and national economies in the developing world. The survival of ß-thalassemia patients solely relies on repeated transfusions, which eventually results into multi-organ damage. The fetal γ-globin genes are ordinarily silenced at birth and replaced by the adult ß-globin genes. However, mutations that cause lifelong persistence of fetal γ-globin, ameliorate the debilitating effects of ß-globin mutations. Therefore, therapeutically reactivating the fetal γ-globin gene is a prime focus of researchers. CRISPR/Cas9 is the most common approach to correct disease causative mutations or to enhance or disrupt the expression of proteins to mitigate the effects of the disease. CRISPR/cas9 and prime gene editing to correct mutations in hematopoietic stem cells of ß-thalassemia patients has been considered a novel therapeutic approach for effective hemoglobin production. However, genome-editing technologies, along with all advantages, have shown some disadvantages due to either random insertions or deletions at the target site of edition or non-specific targeting in genome. Therefore, the focus of this review is to compare pros and cons of these editing technologies and to elaborate the retrospective scope of gene therapy for ß-thalassemia patients.

Immunotherapy and targeted therapy-the new roadmap in cancer treatment.

Immunotherapy is the new frontier in cancer medicine. This manuscript summarizes historical aspect of immunotherapy, particularly its pathway to drug approval as the main therapeutic modality used in clinical medicine. We will discuss the role of immunotherapy in treating various types of cancers and how the treatment landscape once dominated by chemotherapy is rapidly changing.

Molecular pathways and targeted therapy in cholangiocarcinoma.

Cholangiocarcinoma (CCA) encompasses a rare group of malignancies arising from epithelial cells lining the biliary tree that connects the liver and gallbladder to the small intestine. Most patients present with advanced incurable disease that has a poor prognosis, and standard treatment options remain limited. Effective nontoxic treatment options for advanced CCA are needed. Fibroblast growth factors (FGFs) and their fibroblast growth factor receptor (FGFR) pathways are crucial to cellular proliferation, cellular survival, and differentiation of many malignancies, but are especially relevant in CCA. The targeting of FGF/FGFR has become the most promising approach to treating patients with advanced/metastatic CCA. Here we review CCA, and discuss the promise of FGFR-directed therapy in advanced CCA.

Stereotactic body radiation therapy and immunotherapy.

Immunotherapy has revolutionized the treatment of various types of cancers in recent years. Since the US Food and Drug Administration approval of the anti-cytotoxic T-lymphocyte-associated antigen 4 agent ipilimumab for late-stage melanoma in 2011, results from multiple clinical trials have proven the benefit of immunotherapy in the treatment of other cancers. However, therapeutic resistance to immunotherapy often develops. This has led investigators to combine immunotherapy with stereotactic body radiation therapy (SBRT) in an attempt to improve outcomes. The benefit of the combination is believed to stem from stimulating and suppressing various immune pathways and is further aided by the abscopal effect, in which tumors respond to radiation therapy even in nonradiated metastatic sites. When combined with immunotherapy, radiation causes the tumor to act much like a vaccine by exposing the tumor antigens to activate the immune response. This article reviews the association between the immune system and cancer, as well as the additional systemic benefit that SBRT can have in patients with advanced-stage malignancies being treated with immunotherapy.

Supplementation of Cannabis sativa L. leaf powder accelerates functional recovery and ameliorates haemoglobin level following an induced injury to sciatic nerve in mouse model.

Peripheral nerve injury is a common condition with a multitude of signs and symptoms. The major consequence of injury is limited physical activity. Presently, we are lacking effective therapies for PNI and it is need of the hour is to explore potential remedies for the recovery of functional loss. Here, we have investigated the role of crude Cannabis sativa L. leaf powder in promoting functions recovery, in mouse model subjected to a traumatic sciatic nerve injury. A dose of 200mg/kg of the body weight per day was administered orally from the day of nerve crush till the end of the experiment. The motor functions were evaluated by measuring sciatic functional index, muscle grip strength and muscle mass; whereas the sensory functions were assessed by hotplate test. The haematology and serum analyses were carried out to estimate the effect of treatment on the systemic index and oxidative stress. The gain of motor functions was significantly improved and was early noticed in the treated mice. Restoration of muscle mass and elevated haemoglobin level were statistically significant in the treatment group. This study indicates that Cannabis sativa L. supplementation accelerates the motor functions recovery after nerve compression injury.

Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment.

Lung cancer is the major cause for cancer-related death in the US. Although advances in chemotherapy and targeted therapy have improved the outcome of metastatic non-small-cell lung cancer, its prognosis remains dismal. A deeper understanding of the complex interaction between the immune system and tumor microenvironment has identified immune checkpoint inhibitors as new avenue of immunotherapy. Rather than acting directly on the tumor, these therapies work by removing the inhibition exerted by tumor cell or other immune cells on the immune system, promoting antitumoral immune response. To date, two programmed death-1 inhibitors, namely nivolumab and pembrolizumab, have received the US Food and Drug Administration approval for the treatment of advanced non-small-cell lung cancer that failed platinum-based chemotherapy. This manuscript provides a brief overview of the pathophysiology of cancer immune evasion, summarizes pertinent data on completed and ongoing clinical trials involving checkpoint inhibitors, discusses the different strategies to optimize their function, and outlines various challenges that are faced in this promising yet evolving field.

Evaluation of therapeutic control in a Pakistani population with hypertension.

RATIONALE, AIMS AND OBJECTIVES: Cardiovascular diseases (CVD) are increasing at an alarming rate in South Asia. High blood pressure is a modifiable risk factor for CVD. In this study, we evaluated the control of blood pressure and the prevalence of cardiovascular risk factors in patients with hypertension. METHOD: A cross-sectional study was conducted in 50 primary health care centres throughout Pakistan. Individuals with a documented history of hypertension, receiving pharmacological therapy, were enrolled and evaluated for the control of their blood pressure. RESULTS: The recommended therapeutic control of hypertension (systolic blood pressure <140 mmHg, diastolic blood pressure <90 mmHg) was seen in only 6.4% of the study participants. Values of both the mean systolic and diastolic blood pressures in all subjects were higher than the desired therapeutic levels (P<0.001). There was a high prevalence in the study population of established but modifiable risk factors of CVD, such as smoking (30.5%), hypercholesterolemia (59.5%) and sedentary lifestyle (43.5%). Lack of therapeutic control of systolic blood pressure was found significantly associated with age, hypercholesterolemia and sedentary lifestyle (P<0.05). CONCLUSIONS: Patients being treated at primary health care centres in Pakistan have inadequate control of high blood pressure. Evidence-based continuous education of primary health care physicians is a necessary intervention for optimizing treatment strategies and achieving better therapeutic control of hypertension in our population.

Total parotidectomy under local anesthesia: a novel technique.

Parotidectomy is a common procedure usually done for a parotid mass necessitating a histological diagnosis. Operation is normally performed under General anesthesia with a nerve stimulator to facilitate facial nerve stimulation. We describe a new technique with reports of three cases, making total parotidectomy under local anesthesia possible. The ascending cervical branch of cervical plexus and the auriculotemporal nerve were anesthetized by bupivacaine 0.25% (2mg/kg) and lignocaine with adrenaline 7 mg/kg. Effective onset of anesthesia was within 15-25 minutes and the operations lasted between 2-3 hours without any complications. This offers advantage in high-risk patients where general anesthesia is contraindicated. The facial nerve can be easily identified with on command movements by the patient rendering the use of nerve stimulator or injection of the dye superfluous. This technique makes total parotidectomy an outpatient procedure and facilitates an early discharge.

A novel haplotype in ABCA1 gene effects plasma HDL-C concentration.

BACKGROUND AND OBJECTIVES: ATP-binding cassette transporter 1 (ABCA1) is a trans-membrane protein responsible for the efflux of cholesterol and phospholipids across the cell membrane, an essential step in the reverse cholesterol transport system. This study investigates the effect of five non-synonymous SNPs of ABCA1 gene on plasma HDL-C levels in Pakistani individuals free of ischemic heart disease and stroke. METHODS: Five non-synonymous SNPs were selected after sequencing ABCA1 gene in patients of Hypoalphalipoproteinemia. The presence of these SNPs was then checked in 200 individuals by using PCR-RFLP. Plasma glucose and lipid fractions were measured in fasting state. Ethical approval was obtained from the Ethical Review Committee, Aga Khan University and informed consent was obtained from all subjects. RESULTS: LL genotype of V825L polymorphism was associated with decreased levels of HDL-C [-0.17 (-0.32 to -0.19); P=0.02] and P774 allele showed a significant increase in HDL-C levels as compared to T774 allele [-0.15 (-0.18 to -0.02); P=0.01]. R219K, A399V and V771M polymorphisms did not show any association with levels of HDL-C, LDL-C, cholesterol and triglycerides. Haplotype analysis between R219K and V825L polymorphisms showed a unique interaction between R219 allele and L825 allele. The RL haplotype was found to be associated with decreased levels of HDL-C [-0.12 (-0.22 to -0.03); P=0.001]. CONCLUSIONS: ABCA1 polymorphisms are associated with varying levels of HDL-C in Pakistani individuals. These results warrant further investigations as ABCA1 polymorphisms may have a major role in the high incidence of cardiovascular disorders in South Asians.