Alternative Treatment Research Articles

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Congenital Syphilis - Comprehensive Narrative Review of Alternative Antibiotic Treatment for Use in Neonates.

Congenital syphilis rates increased 10-fold from 2012 to 2022 in the United States. Currently, the therapeutic standard of care is 10 days of intravenous (IV) aqueous crystalline penicillin G, with very limited evidence for alternatives. A long course of IV antibiotic requires hospitalization that is both costly and burdensome for the child and the family. Fortunately, T. pallidum retains susceptibility to other antibiotics based on minimum inhibitory concentrations (MICs). Based on the evidence of safety and efficacy of different antibiotics for use in neonates, ceftriaxone emerges as a potential parenteral candidate and amoxicillin emerges as a potential oral candidate for the treatment of congenital syphilis. Other therapeutic alternatives include cefotaxime (where available), ampicillin, doxycycline, cefixime, and linezolid.

Therapeutic Phage Candidates for Targeting Prevalent Sequence Types of Carbapenem-Resistant Escherichia coli.

Carbapenem-resistant Escherichia coli (CREC) is a global threat to public health; therefore, alternative treatment options are urgently needed. Bacteriophages have emerged as promising candidates for combating CREC infections. This study aimed to investigate the genetic basis of phage sensitivity in CREC by evaluating carbapenem resistance among multidrug-resistant (MDR) E. coli isolated in Daegu, South Korea and analyzing their sequence types (STs) with phage susceptibility spectra. Among the 60 MDR E. coli isolates, 80.4% were identified as CREC, with 77.0% demonstrating resistance to imipenem and 66.6% to meropenem. Moreover, 70 lytic E. coli bacteriophages were isolated from hospital sewage water and evaluated against those 60 E. coli isolates. The phages exhibited lytic activity of 33%-60%, with average titers ranging from 5.6 × 1012 to 2.4 × 1013 PFU/mL (Plaque-Forming Unit). Furthermore, multilocus sequence typing (MLST) analysis of the bacterial isolates revealed 14 distinct STs, mostly belonging to ST131, ST410, and ST648. Notably, the phage susceptibility spectra of ST73, ST13003, ST648, ST2311, ST167, ST405, ST607, ST7962, and ST131 were significantly different. Thus, the isolated phages can effectively lyse CREC isolates, particularly those with clinically dominant STs. Conversely, ST410 exhibited a 14.2%-87.14% susceptibility spectrum, whereas ST1139, ST1487, ST10, and ST206 did not lyse, suggesting the presence of more resistant STs. Future studies are warranted to identify the reasons behind this resistance and address it. Ultimately, this study will aid in developing focused treatments to address these pressing global health issues.

Hypnotics on Obstructive Sleep Apnea Severity and Endotypes: A Systematic Review and Meta-Analysis.

Low arousal threshold and poor muscle responsiveness are common determinants of obstructive sleep apnea (OSA). Hypnotics were hypothesized as an alternative OSA treatment via raising the arousal threshold and possibly genioglossus responsiveness. Effect of common hypnotics on arousal threshold, OSA severity and genioglossus responsiveness. We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov for randomized clinical trials, and ran meta-analyses to determine the effect of oral hypnotics on arousal threshold, OSA severity and genioglossus responsiveness. GRADE was used to rate the quality of evidence (QoE). The association between post-treatment AHI and arousal threshold percent reductions was explored in individual patient data (IPD) metanalyses (overall sample and low arousal threshold subgroups). Based on our analysis (27 studies; 25 for AHI, 11 for arousal threshold, 4 for genioglossus responsiveness), hypnotics minimally raised arousal threshold (mean difference [95% CI]: 2.7 [1.5, 3.8] cmH2O epiglottic pressure swings; moderate QoE), but did not change OSA severity (1.4 [3.5, 0.7] events/h; moderate QoE). IPD meta-analysis (N=114) showed no association between changes in arousal threshold and AHI, independent of low arousal threshold subgrouping. However, people with very-low arousal threshold or those who exhibited 0-25% arousal threshold increase from placebo experienced the greatest-yet still modest-post-treatment AHI reductions (10%). Hypnotics did not affect genioglossus responsiveness (high QoE). Further research testing or clinical use of hypnotics as OSA alternative treatments should be discouraged, unless in the presence of comorbid insomnia or as part of combination therapy in individuals with very-low arousal threshold.

Poly-β-hydroxybutyrate supplementation enhanced the growth and immune responses of juvenile Nile tilapia (Oreochromis niloticus)

Development of alternative disease treatment and prevention strategies has received considerable attention in recent years due to frequent epizootic outbreaks in modern intensive aquaculture. Poly-β-hydroxybutyrate (PHB) is a biopolymer synthesized by some bacteria with potential immunostimulatory effects. This study analyzed the potential of PHB as an immunomodulator in juvenile Nile tilapia utilizing in vitro and in vivo approaches. Head-kidney-derived macrophage production of intra- and extra-cellular superoxide anion exhibited significant linear and quadratic relationships with graded doses (0.0, 0.5, 1.0, 2.0, 4.0 and 8.0 mM) of a PHB precursor, 3-hydroxybutryate (3HB). Additionally, lyophilized PHB-synthesizing bacteria, Zobellella denitrificans (ZD1), were supplemented to a practical basal diet for Nile tilapia (36% crude protein and 6% crude lipid) to produce five isonitrogenous and isolipidic experimental diets containing PHB in five stepwise increments (0.125, 0.25, 0.5, 1.0, and 2.0% of dry-diet weight). After termination of the feeding trial, Nile tilapia exhibited dose-dependent linear and quadratic relationships in percentage weight gain, as well as feed efficiency, protein conversion efficiency, and hepatosomatic index. Finally, PHB-supplemented diets did significantly modulate intestinal microbiota composition. In conclusion, Nile tilapia exhibited enhanced growth parameters, condition factors, immunological responses, and intestinal microbiota modulation when fed PHB, with the optimal inclusion level determined to be 1% of dry diet.

Implementation fidelity of intravenous ferric carboxymaltose administration for iron deficiency anaemia in pregnancy: a mixed-methods study nested in a clinical trial in Nigeria

BackgroundIron deficiency anaemia is common among pregnant women in Nigeria. The standard treatment is oral iron therapy, which can be sub-optimal due to side effects. Intravenous ferric carboxymaltose (FCM) is an evidenced-based alternative treatment with a more favourable side effect profile requiring administration according to a standardized protocol. In this study, we assessed the fidelity of administering a single dose of FCM according to protocol and identified factors influencing implementation fidelity.MethodsWe used a mixed-method approach with a sequential explanatory design nested in a clinical trial across 11 facilities in Lagos and Kano States, Nigeria. Guided by a conceptual framework of implementation fidelity, we quantitatively assessed adherence to protocol by directly observing every alternate FCM administration, using an intervention procedure checklist, and compared median adherence by facility and state. Qualitative fidelity assessment was conducted via in-depth interviews with 14 skilled health personnel (SHP) from nine purposively selected health facilities, using a semi-structured interview guide. We analyzed quantitative data using descriptive and inferential statistics in Stata and used thematic analysis to analyze the transcribed interviews in NVivo.ResultsA total of 254 FCM administrations were observed across the 11 study sites, with the majority in secondary (63%), followed by primary healthcare facilities (PHCs) (30%). Overall, adherence to FCM administration as per protocol was moderate (63%) and varied depending on facility level. The lowest level of adherence was observed in PHCs (36%). Median, adherence level showed significant differences by facility level (p = 0.001) but not by state (p = 0.889). Teamwork and availability of protocols are facilitation strategies that contributed to high fidelity. However, institutional/ logistical barriers are contextual factors that influenced the varied fidelity levels observed in some facilities.ConclusionsCollaborative teams and access to operating protocols resulted in high fidelity in some facilities. However, in some PHCs, fidelity to FCM was low due to contextual factors and intervention complexities, thereby influencing the quality of delivery. In Nigeria, scale-up of FCM will require attention to staff strength, teamwork and availability of administration protocols, in order to optimize its impact on anaemia in pregnancy.

Adverse Events with Hypoglossal Nerve Stimulation in the Treatment of Obstructive Sleep Apnea—A Systematic Review of Clinical Trials and Real-World Data

Background/Objectives: Hypoglossal nerve stimulation (HNS) emerged as an alternative treatment for patients with obstructive sleep apnea (OSA) a decade ago. Long-term clinical trials and real-world data show that HNS treatment provides significant and sustained improvements in both OSA disease control and quality-of-life measures over time. Given the nature of HNS treatment, with the requirement of using an implantable neurostimulation system, patient safety is a critical domain in the assessment of this technology. The objective of this review was to evaluate adverse events (AEs) and complications with HNS therapy in a systematic review of published evidence. Methods: Medline, Cochrane, and Web of Science were systematically searched to identify randomized controlled and real-world observational studies reporting relevant outcomes with HNS therapy for treatment of OSA that included procedure-, device-, and treatment-related AEs. Results: Out of 418 articles screened, 27 were reviewed for eligibility, and 17 studies, the majority found to have low-to-moderate risk of bias, with data on 1962 patients were included for further analysis. Across included studies, reporting of AEs was heterogeneous with regard to the classifications used and the extent of reporting. Over an average follow-up duration of 17.5 ± 16.9 months, the pooled mortality rate was 0.01% (95% CI = 0.0 to 0.2%), with all reported deaths being unrelated to HNS treatment. The HNS system survival probability over the follow-up time of 60 months was 0.9834 (95% CI = 0.9768 to 0.9882), with infections and request for removal by patients being the most common indications. The pooled surgical revision rate was 0.08% (95% CI 0.0 to 0.2%). Most reported treatment-related side effects were transient stimulation-related discomfort (0.08%, 95% CI = 0.0 to 0.2%) and tongue abrasions (0.07%, 95% CI = 0.0 to 0.2%). Based on the systematic review, a standardized set of endpoints was defined, aiming to harmonize safety data relevant to HNS therapy. Conclusions: In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation and during the treatment acclimatization period. Due to a lack of available evidence, partially implantable HNS systems are underrepresented in this review, which limits the generalizability of the results. Significant heterogeneity was found for adverse event reporting. A framework for reporting HNS outcomes that includes AEs and side effects is proposed to facilitate comparability of the reported data.

Impact of primary endoscopic resection on oncological outcomes after esophagectomy for cancer: a retrospective propensity score-based cohort study.

Esophageal cancer posed significant global health challenges, particularly due to poor survival rates, especially in advanced stages. Primary endoscopic resection had emerged as an alternative treatment for early esophageal cancer, aiming to preserve organ function and reduce surgical morbidity. This retrospective multicenter cohort study included 334 patients with early esophageal cancer (T1a-b, N0) from 30 French-speaking European centers between 2000 and 2010. Patients underwent either primary endoscopic resection followed by esophagectomy (E group, n = 36) or esophagectomy alone (S group, n = 298). Cox proportional hazards models adjusted for TNM stage and propensity score weighting were used to assess the impact of primary endoscopic resection on recurrence-free survival (RFS), overall survival (OS), and postoperative complications. Primary endoscopic resection did not significantly influence RFS (adjusted HR 0.92, 95% CI 0.31 to 2.68, p = 0.88) or OS (adjusted HR 1.06, 95% CI 0.35 to 3.13, p = 0.92) compared to esophagectomy alone. Initial higher thromboembolic complications in the endoscopic resection group were not significant after adjustment (adjusted OR 4.73, 95% CI 0.34 to 64.27, p = 0.24). Primary endoscopic resection followed by esophagectomy for early esophageal cancer did not alter oncological outcomes or overall survival in this retrospective cohort. These findings supported the role of primary endoscopic resection as a safe initial treatment strategy, warranting validation in larger prospective studies. Our study was registered retrospectively on the Clinicaltrials.com website under the identifier NCT01927016. We acknowledge the importance of prospective registration and regret that this was not done before the commencement of the study.

Real-World Experience of Fluocinolone Acetonide 0.19 mg in the Management of Non-Infectious Uveitis

ABSTRACT Purpose This study aims to evaluate the real-world efficacy and safety profile of fluocinolone acetonide (FAc) implants for the treatment of non-infectious uveitis (NIU). Methods A retrospective, observational study was conducted at Moorfields Eye Hospital, London, involving patients who received FAc 0.19 mg implants (Iluvien®) for NIU. 2-year follow-up data on baseline characteristics, indications, and outcomes was collected. The primary indicator for treatment failure was defined as the need for rescue treatment with dexamethasone (DEX) implants, while secondary indicators included changes in steroid and systemic immunosuppression requirements, or the need for a second FAc implant before 3 years. The occurrence of complications was collected. Results Of the 146 eyes treated with FAc implants, 24.0% experienced treatment failure requiring DEX implant within 2 years. About 42.9% required this within the first 6 months. There was an increase in the number of patients requiring steroids and/or systemic immunosuppression. Within the first 2 years post-FAc implant, only 13.7% experienced an IOP rise, with 4.1% requiring IOP-lowering surgery. About 57.9% of the phakic eyes developed cataracts. Conclusion This study provides valuable real-world evidence supporting the efficacy of FAc implant in NIU. It demonstrates a good safety profile at 2 years, with a significant reduction in uveitis recurrence rate and treatment burden. Our results are especially pertinent to the treatment of uveitic cystoid macular oedema (CMO), which was the primary indication in over 75% of our patients. Furthermore, it suggests that while FAc implant controls retinal inflammation effectively, choroidal inflammation would require alternative treatment.

Industrial Catalytic Production Process of Erythromycin

The impact of COVID-19’s unexpected outbreak forced the scientific community to seek alternative treatment methods in order to overcome the hindrance of traditional medicine in terms of alleviating the symptoms of this virus. Erythromycin, which was introduced in 1952, is an antibiotic that is reported to pose as an effective substitute medication for various ailments such as skin, respiratory, bone, and female reproductive conditions, and cancer, as well as the newly added COVID-19. The importance of both the erythromycin molecule and the catalyst of its production, namely P450eryF of the cytochrome P450 family, in many health-concerned and environmentally related applications, has led several countries, the World Health Organization (WHO) and the health industry to recruit and cooperate with numerous universities and institutions, in an attempt to tackle the demand for efficient antibiotics. The aim of this study is to discuss and further analyze the overall structure and catalytic mechanism of erythromycin’s synthesis and industrial production, in order to gain a better comprehension of this molecule’s significance and value in the pharmaceutical field. This was carried out through the citation of the current production rates per country and the latest statistics and published patents. As implied in this manuscript, the demand for an increase and improvement in the production of erythromycin and its antibiotic derivatives should be globally promoted to deliver more effective results against infectious diseases, such as COVID-19.

Needle-free jet injector treatment with bleomycin is efficacious in patients with severe keloids: a randomized, double-blind, placebo-controlled trial.

Severe keloids are difficult to treat. Corticosteroid injections with needles are painful and associated with frequent recurrences. Therefore, more effective, safe and patient friendly alternative treatments are urgently needed. To assess the efficacy, tolerability, and patient satisfaction of intralesional bleomycin treatment using a needle-free electronic pneumatic jet injector (EPI) in severe keloids. Patients with severe keloids were included in this double-blind, randomized placebo-controlled trial with split-lesion design. Three EPI treatments with bleomycin or saline, were administered every four weeks in respectively the intervention and control side. Outcome measures were change in scar volume assessed by 3D-imaging, Patient and Observer Scar Assessment Scale (POSAS), skin perfusion with laser speckle contrast imaging (LSCI), spilled volume, procedure related pain, adverse events, and patient satisfaction. Fourteen patients (9 female, 5 men) were included. The estimated mean keloid volume was significantly reduced with 20% after EPI-assisted bleomycin, compared to a slight increase of 3% in the control side (p<0.01). The estimated mean POSAS patient and observer scores decreased with respectively 26% and 28% (p = 0.02; p = 0.03). LSCI showed no significant change in perfusion. EPI treatment was preferred over previous needle injections in 85% of patients. The estimated mean spilled volume after EPI was around 50%, and NRS pain scores were moderate. Adverse events included bruising, hyperpigmentation, and transient superficial necrosis. Three EPI-assisted bleomycin treatments are efficacious and well-tolerated in severe keloids. Moreover, EPI treatment was preferred by most patients and may serve as a patient-friendly alternative treatment.

Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives.

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

OKN-007 is an Effective Anticancer Therapeutic Agent Targeting Inflammatory and Immune Metabolism Pathways in Endometrial Cancer.

Advanced-stage endometrial cancer patients typically receive a combination of platinum and paclitaxel chemotherapy. However, limited treatment options are available for those with recurrent disease, and there is a need to identify alternative treatment options for the advanced setting. Our goal was to evaluate the pre-clinical efficacy and mechanism of action of Oklahoma Nitrone 007 (OKN-007) alone and in combination with carboplatin and paclitaxel in endometrial cancer. The effect of OKN-007 on the metabolic viability of endometrial cancer cells in both two- and three-dimensional (2D and 3D) cultures, as well as on clonogenic growth, in vitro was assessed. We also evaluated OKN-007 in vivo using an intraperitoneal xenograft model and targeted gene expression profiling to determine the molecular mechanism and gene expression programs altered by OKN-007. Our results showed that endometrial cancer cells were generally sensitive to OKN-007 in both 2D and 3D cultures. OKN-007 displayed a reduction in 3D spheroid and clonogenic growth. Subsequent targeted gene expression profiling revealed that OKN-007 significantly downregulated the immunosuppressive and immunometabolic enzyme indolamine 2,3-dioxygenase 1 (IDO1) (-11.27-fold change) and modulated upstream inflammatory pathways that regulate IDO1 expression (interferon- (IFN-), Jak-STAT, TGF-β, and NF-kB), downstream IDO1 effector pathways (mTOR and aryl hydrocarbon receptor (AhR)) and altered T-cell co-signaling pathways. OKN-007 treatment reduced IDO1, SULF2, and TGF-β protein expression in vivo, and inhibited TGF-β, NF-kB, and AhR- receptor-mediated nuclear signaling in vitro. These findings indicate that OKN-007 surmounts pro-inflammatory, immunosuppressive, and pro-tumorigenic pathways and is a promising approach for the effective treat endometrial cancer. Significance Statement Women with advanced and recurrent endometrial cancer have limited therapeutic options. OKN-007, which has minimal toxicity and is currently being evaluated in early-phase clinical trials for the treatment of cancer, is a potential new strategy for the treatment of endometrial cancer.

Carbapenem-resistant Acinetobacter baumannii infections among diabetic and non-diabetic patients and possible effective combination treatments

BackgroundCarbapenems are one of the most noteworthy choices for treating multidrug-resistant Acinetobacter baumannii (A. baumannii). Currently, carbapenem-resistant A. baumannii (CRAB) represents a healthcare problem worldwide, particularly among diabetic patients who are more susceptible to microbial infections. The aim of this study was to investigate the differences in antibiotic susceptibility profiles, the abundance of carbapenem resistance genes across A. baumannii-infected diabetic and non-diabetic patients, and the antimicrobial activity of different antibiotic combinations on highly resistant isolates.MethodsData of 99 A. baumannii-infected patients were collected during the period from 2018 to 2022 and categorized according to patients’ diabetes status into either diabetic or non-diabetic group. A total of 45 A. baumannii isolates were collected during 2021 and 2022 from the main hospital laboratory to be reidentified and genetically confirmed. Antibiotic susceptibility, including carbapenems, was determined using disc agar diffusion and broth microdilution methods. The isolates were screened for OXA-23, GES, VIM, and NDM carbapenem-resistant genes. Five antibiotic combinations were assessed using the double-disk synergy and checkerboard methods.ResultsThe findings of the current study revealed that multidrug resistance increased gradually, from 56% in 2018 to 95.6% in 2022. Moreover, CRAB increased among diabetics and non-diabetics. Resistance rates of imipenem, meropenem, and doripenem reached 68.8%, 61.8%, and 47.4% in diabetics and 97.9%, 83.3%, and 50% in non-diabetics, respectively. The VIM gene was the most prevalent gene with prevalence rates of 100% and 96.15% in diabetics and non-diabetics, respectively. Moreover, all A. baumannii isolates carried at least two of the selected carbapenem-resistant genes. Across the different used combinations, only the tigecycline-meropenem combination showed synergistic activity in 50% of diabetic and 66.7% of non-diabetic isolates.ConclusionsAn increased carbapenem resistance was observed among A. baumannii-infected individuals, both diabetic and non-diabetic. The MEM/TCG combination was the only one that showed synergistic or additive effects against highly resistant isolates making it a viable alternative treatment option.

Treatment of infections caused by carbapenem-resistant Acinetobacter baumannii

Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drugs can alleviate or prevent the effects of CRAB infections, shorten hospital stays, and reduce patient mortality.

The mechanics of tissue-engineered temporomandibular joint discs: Current status and prospects for enhancement.

The temporomandibular joint (TMJ) disc is an essential protective but vulnerable fibrocartilage. Their high mechanical strength is vital in absorbing loads, reducing friction, and protecting the condylar surface. Many diseases can lead to the destruction or degeneration of the mechanical function of the TMJ disc. Unfortunately, conservative treatment is ineffective in restoring the defective mechanical properties of the discs. Tissue engineering has been investigated as a promising alternative treatment approach to approximate the properties of native tissue. However, it is difficult for tissue-engineered discs to obtain sufficient mechanical properties. Several approaches have been proposed to improve the mechanical properties of tissue-engineered constructs. In this review, we summarized the mechanical properties of native TMJ discs and discussed the current mechanical testing methods. We then summarized the current advances in improving the mechanical properties of TMJ disc tissue-engineered constructs. Moreover, existing challenges and outbreak directions are discussed. This review assists future research in better understanding the mechanical properties of both native and tissue-engineered TMJ discs. It provides new insights into future mechanical property enhancement for TMJ disc tissue engineering.

Feasibility of Nanostructured Lipid Carrier Loaded with Alpha-Mangostin and Clove Oil for Canine Periodontal Therapy

Nanostructured lipid carriers (NLC) represent the second generation of nanoparticles, offering numerous advantages over conventional delivery systems. These include improved stability, enhanced drug-loading capacity, and controlled release profiles, making them highly attractive candidates for a wide range of therapeutic applications. Their suitability for hydrophobic drugs like a traditional medicinal plant of Thailand as clove oil and alpha-mangostin. We investigated into nanostructured lipid carriers loaded with Alpha-Mangostin and clove oil (NLC-AMCO) into the physicochemical and biological characteristics to identify the formulation with the highest efficacy for treatment. The particle size, charge, polydispersity index, and other characterizations were recorded. The realtime ex vivo penetration was explored using canine gingival tissue. Drug sustained release was assessed by HPLC. Moreover, the antibacterial properties were tested by conventional methods. The NLC-AMCO can be stored at up to 40 °C for 60 days without any alterations in particle characteristics. Gingival tissue penetration and sustained drug release were superior compared to unencapsulated counterparts. It exhibited greater effectiveness in inhibiting bacterial growth than the antibiotics tested, particularly against bacteria from the oral cavities of dogs. Therefore, this alternative treatment approach offers cost-effectiveness and ease of administration for pet owners and reduces discomfort for the animals during restraint.

Antagonistic and antibacterial activity of &lt;i&gt;Lactobacillus rhamnosus&lt;/i&gt; HN001 and &lt;i&gt;Lactobacillus acidophilus&lt;/i&gt; La-14 included in the oral probiotic

BACKGROUND: A microbial imbalance in the vaginal biotope leads to the development of vaginal infections and is associated with urinary tract infections. The ineffectiveness of the therapy and the frequent recurrence of these infections are important reasons for searching for alternative treatment strategies. A progressive solution to this issue has been the use of oral probiotics with a targeted effect on the intestinal and vaginal microflora. AIM: The aim of this study was to evaluate the antagonistic and antibacterial activity of the probiotic strains Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14, which are the components of the oral probiotic, against opportunistic microorganisms of intestinal origin, while assessing the sensitivity of these strains to antimicrobial drugs. MATERIALS AND METHODS: The probiotic strains Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14 included in the oral probiotic Duogynal® were cultivated and the grown colonies were identified using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method (Bruker Daltonics GmbH Co., Germany). To study the antagonism of the probiotic strains of lactobacilli and opportunistic pathogenic microorganisms, the following 11 clinical isolates were collected: Escherichia coli (two isolates), Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter asburiae, Proteus mirabilis, Citrobacter freundii, Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, and Candida albicans. To assess the sensitivity of the probiotic strains to antimicrobial drugs, the Gram Positive AST panel (Autobio Diagnostics Co., Ltd, China) was used. RESULTS: When the microorganisms were co-cultivated with the probiotic lactobacilli (Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14), we noted a decrease in pH and the death of opportunistic microorganisms such as Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter asburiae, Proteus mirabilis, Citrobacter freundii, Staphylococcus aureus, Enterococcus faecalis, and Streptococcus agalactiae, as well as yeast-like fungi Candida albicans. When studying antibiotic resistance, it was found that the both strains of lactobacilli were resistant to ampicillin, vancomycin, daptomycin, clindamycin, linezolid, moxifloxacin, nitrofurantoin, oxacillin, oritavancin, penicillin, rifampin, teicoplanin, tigecycline, trimethoprim/sulfamethoxazole, cefoxitin, ceftarolin, and ciprofloxacin. CONCLUSIONS: The oral probiotic, which contains a combination of two lactobacilli (Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14), has pronounced antagonistic activity against opportunistic microorganisms. These strains are resistant to most antibacterial drugs used in widespread clinical practice, which may be the basis for recommending the use of this probiotic drug together with prescribed antibiotics for prevention of vaginal or intestinal dysbiosis.

The efficacy of cone-beam computed tomography-guided transcatheter arterial chemoembolization in hepatocellular carcinoma survival: A systematic review

Cone-beam computed tomography (CBCT)-guided transcatheter arterial chemoembolization (TACE) represents an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients, yet a comprehensive evaluation of CBCT guidance on this procedure and CBCT’s impact on patient survival remains lacking. We aimed to assess the efficacy and benefits of CBCT-guided TACE in improving survival outcomes for patients with HCC and show the importance of CBCT in interventional radiology. Meta-analysis was conducted to evaluate CBCT-guided TACE compared to conventional TACE in the treatment of HCC. PubMed and Cochrane library databases were searched for studies published. Outcomes of interest included 1- or 3-year local progression-free survival (LPFS) rates, overall survival (OS) rates, and tumor response results. A total of eight studies were included in the meta-analysis, comprising 1176 patients. The analysis showed that CBCT-guided TACE improved 1-year LPFS (odds ratio [OR] = 2.81, P &lt; 0.001), 3-year (OR = 4.42, P = 0.002), and the 3-year OS rates (OR = 3.03, Confidence Interval = 1.65–11.80, P = 0.14) compared to conventional TACE. CBCT-guided TACE enhances survival outcomes for patients with HCC; by addressing this research gap, our study endeavors to encourage clinicians and researchers to pursue this medical technology by providing a robust synthesis of current evidence.