Revisiting the Evidence Base Informing the Use of Adjunctive Therapy for Enterococcus faecalis Endocarditis: A Systematic Review and Meta-Analysis.

BACKGROUND: Current guidelines recommend adjunctive gentamicin for the treatment of Enterococcus faecalis infective endocarditis (EFIE) despite a risk of toxicity. We sought to revisit the evidence for adjunctive therapy in EFIE and to synthesize the comparative safety and effectiveness of adjunctive use of the aminoglycosides versus ceftriaxone by systematic review and meta-analysis. METHODS: For historical context, we reviewed the seminal case series and in vitro studies informing the evolution from penicillin monotherapy to modern-day regimens for EFIE. Next, we searched MEDLINE and Embase from inception to January 16, 2024 for studies of EFIE comparing 1) adjunctive aminoglycosides versus ceftriaxone or 2) adjunctive therapy versus monotherapy. Where possible, clinical outcomes were compared between regimens by random-effects meta-analysis. Otherwise, data were narratively summarized. RESULTS: Results for the systematic review and meta-analysis were limited to 10 observational studies totaling 911 patients. All studies were at high risk of bias. Relative to adjunctive ceftriaxone, gentamicin had similar all-cause mortality (Risk Difference [RD]=-0.8%, 95% Confidence interval [95%CI]=-5.0, 3.5), relapse (RD=-0.1%, 95%CI=-2.4, 2.3), and treatment failure (RD=1.1%, 95%CI=-1.6, 3.7), but higher discontinuation due to toxicity (RD=26.3%, 95%CI=19.8, 32.7). The 3 studies comparing adjunctive therapy to monotherapy included only 30 monotherapy patients and heterogeneity precluded meta-analysis. CONCLUSION: Adjunctive therapy with ceftriaxone appeared to be equally effective and less toxic than gentamicin for the treatment of EFIE. The existing evidence does not clearly establish the superiority of either adjunctive therapy or monotherapy. Pending randomized evidence, if adjunctive therapy is to be used, ceftriaxone appears to be a reasonable option.

Adjunctive Surgery Is Often Without Oncological Benefit at Time of Postchemotherapy Retroperitoneal Lymph Node Dissection.

PURPOSE: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumors (GCTs) aims to resect all remaining metastatic tissue. Resection of adjacent visceral or vascular organs is commonly performed for complete resection. Resection of organs harboring only necrosis results in relevant overtreatment. The study aimed to describe the frequency of metastatic involvement of resected organs with teratoma or viable cancer and to analyze perioperative complications and relapse-free survival. MATERIALS AND METHODS: In a 2-center study, we reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 and identified 242 (20%) cases of adjunctive surgery during PC-RPLND. We analyzed the removed adjacent structures and the pathohistological presence of GCT elements in the resected organs: viable GCT, teratoma, or necrosis/fibrosis. Surgery-associated complications were reported according to the Clavien-Dindo classification. RESULTS: Viable GCT, teratoma, and necrosis were present in 54 (22%), 94 (39%), and 94 (39%), respectively, of all patients with adjunctive resection of adjacent organs. Vascular resections or reconstructions (n = 112; viable: 23%, teratoma: 41%, necrosis: 36%) were performed most frequently, followed by nephrectomies (n = 77; viable: 29%, teratoma: 39%, necrosis: 33%). Perioperative complications of grade ≥ IIIa occurred in 6.6% of all patients, with no difference between the viable GCT and teratoma/necrosis groups (P = .1). A total of 76 patients have been followed without a relapse for at least 36 months. Median follow-up of the whole cohort was 22 months (quartile 7 and 48). Patients with viable GCT/teratoma in the resected specimens had a significantly increased risk of recurrence by 5 years compared to patients with only necrosis (19% vs 59% vs 81%, P < .001). CONCLUSIONS: This study shows that 33% to 40% of all resections of adjacent organs do not harbor teratoma or viable GCT. This highlights the need for better patient selection for these complex patients.

Potassium-lowering effects of sodium zirconium cyclosilicate in the early post-transplant period.

PROBLEM: Hyperkalemia is a serious condition among intra-abdominal transplant recipients, and the safety and efficacy of sodium zirconium cyclosilicate (SZC) for its management during the early post-transplant period are not well-established. METHODS: Adults who received at least one 10-g dose of SZC within 14 days after an intra-abdominal transplant between January 2020 and July 2022 were included in our study. The primary outcome was the change in potassium (K+) levels following the first SZC dose. Other analyses explored adjunctive potassium-lowering therapies, potential gastrointestinal complications, and patient subgroups based on therapy and transplant type. RESULTS: Among the recipients (n = 46), 11 were kidney recipients, 26 were liver recipients, seven were simultaneous liver/kidney recipients, and two were simultaneous pancreas/kidney recipients. The mean time to first dose post-transplant was 7.6 (±4) days, and the mean change in serum K+ after the initial SZC dose was -.27 mEq (p = .001). No gastrointestinal complications were observed following the SZC dose. The mean increase in serum bicarbonate was .58 mEq (p = .41) following the first dose of SZC. Four kidney recipients required dialysis following the SZC dose. CONCLUSION: This study represents the largest investigation on the use of SZC in transplant recipients. A single 10-g dose of SZC reduced serum K+ levels in all subgroups, while the use of adjunctive K+-lowering therapies did not provide additional reduction beyond the effects of SZC. Importantly, no gastrointestinal complications were observed. These findings suggest that SZC may be a safe and promising therapeutic option for hyperkalemia management following solid organ transplantation.

Improving Delivery and Use of HIV Pre-Exposure Prophylaxis in the US: A Systematic Review of Implementation Strategies and Adjunctive Interventions.

Implementation of pre-exposure prophylaxis (PrEP) to prevent HIV transmission is suboptimal in the United States. To date, the literature has focused on identifying determinants of PrEP use, with a lesser focus on developing and testing change methods to improve PrEP implementation. Moreover, the change methods available for improving the uptake and sustained use of PrEP have not been systematically categorized. To summarize the state of the literature, we conducted a systematic review of the implementation strategies used to improve PrEP implementation among delivery systems and providers, as well as the adjunctive interventions used to improve the uptake and persistent adherence to PrEP among patients. Between November 2020 and January 2021, we searched Ovid MEDLINE, PsycINFO, and Web of Science for peer reviewed articles. We identified 44 change methods (18 implementation strategies and 26 adjunctive interventions) across a variety of clinical and community-based service settings. We coded implementation strategies and adjunctive interventions in accordance with established taxonomies and reporting guidelines. Most studies focused on improving patient adherence to PrEP and most conducted pilot trials. Just over one-third of included studies demonstrated a positive effect on outcomes. In order to end the human immunodeficiency virus (HIV) epidemic in the U.S., future, large scale HIV prevention research is needed that develops and evaluates implementation strategies and adjunctive interventions for target populations disproportionately affected by HIV.

Effectiveness of pulse methylprednisolone in patients with non-human immunodeficiency virus pneumocystis pneumonia: a multicentre, retrospective registry-based cohort study.

BACKGROUND: A recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP. METHODS: This multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500-1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure. RESULTS: The study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (14.2% vs. 15.5%, P = 0.850) and 180-day mortality (33.5% vs. 27.3%, P = 0.516) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure. CONCLUSIONS: After adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP.

Enhanced immunomodulation and periodontal regeneration efficacy of subgingivally delivered progranulin-loaded hydrogel as an adjunct to non-surgical treatment for Class II furcation involvement in dogs.

AIM: To evaluate the effect of subgingival delivery of progranulin (PGRN)/gelatin methacryloyl (GelMA) complex as an adjunct to scaling and root planing (SRP) on an experimental periodontitis dog model with Class II furcation involvement (FI). MATERIALS AND METHODS: A Class II FI model was established, and the defects were divided into four treatment groups: (a) no treatment (control); (b) SRP; (c) SRP + GelMA; (d) SRP + PGRN/GelMA. Eight weeks after treatment, periodontal parameters were recorded, gingival crevicular fluid and gingival tissue were collected for ELISA and RT-qPCR, respectively, and mandibular tissue blocks were collected for micro computed tomography (micro-CT) scanning and hematoxylin and eosin (H&E) staining. RESULTS: The SRP + PGRN/GelMA group showed significant improvement in all periodontal parameters compared with those in the other groups. The expression of markers related to M1 macrophage and Th17 cell significantly decreased, and the expression of markers related to M2 macrophage and Treg cell significantly increased in the SRP + PGRN/GelMA group compared with those in the other groups. The volume, quality and area of new bone and the length of new cementum in the root furcation defects of the PGRN/GelMA group were significantly increased compared to those in the other groups. CONCLUSIONS: Subgingival delivery of the PGRN/GelMA complex could be a promising non-surgical adjunctive therapy for anti-inflammation, immunomodulation and periodontal regeneration.

Decision-making on systemic antibiotics in the management of periodontitis: A retrospective comparison of two concepts.

AIM: To retrospectively compare two approaches for the adjunctive use of systemic antibiotics in non-surgical periodontal therapy: one based on the detection of Aggregatibacter actinomycetemcomitans (Aa) and the other on age and severity of periodontitis (Age & PPD). We also assessed the additional benefit of antibiotics in reducing the need for further surgical therapy in each group. MATERIALS AND METHODS: Patients of the Department of Periodontology, Goethe University Frankfurt, Germany, were screened for microbiological testing between 2008 and 2018. Patients were categorized by their microbiological result (Aa+/-) and demographic/clinical data (Age & PPD+/-). Agreement on antibiotic indication was tested. The clinical evaluation focussed on teeth with probing pocket depths (PPDs) ≥ 6 mm. RESULTS: Analysis of 425 patients revealed 30% categorized as Age & PPD+ and 34% as Aa+. Sixty-three percent had consistent antibiotic recommendations (phi coefficient 0.14, p = .004). Patients in the Age & PPD+ group receiving antibiotics showed the most substantial reduction in the number of teeth with PPD ≥ 6 mm after non-surgical periodontal therapy. CONCLUSIONS: Both strategies resulted in a significant clinical improvement compared with those without antibiotic treatment and restricted antibiotic use similarly, but targeted different patient groups. Younger individuals with severe periodontitis benefited most from antibiotics, reducing the need for additional surgeries. The study was registered in an international trial register (German Clinical Trial Register number DRKS00028768, registration date 27 April 2022, https://drks.de/search/en/trial/DRKS00028768).

The Influence of Personality Disorder Symptoms on Treatment Outcomes in Bipolar Disorder: A Secondary Analysis of a Randomised Controlled Trial: L'influence des symptômes du trouble de la personnalité sur les résultats du traitement dans le trouble bipolaire : Une analyse secondaire d'un essai randomisé contrôlé.

OBJECTIVES: Many people who are diagnosed with bipolar disorder also have comorbid personality disorder. Few studies have explored how personality disorder may influence pharmacological treatment outcomes. The aim of this study was to conduct a secondary analysis of data from a clinical trial of adjunctive nutraceutical treatments for bipolar depression, to determine whether maladaptive personality traits influence treatment outcomes. METHODS: Scores on the Standardised Assessment of Personality - Abbreviated Scale screener were used to classify participants as having bipolar disorder with (n = 119) and without (n = 29) above threshold personality disorder symptoms (personality disorder). Outcome measures included: The Montgomery Åsberg Depression Rating Scale, Clinical Global Impressions and Improvement Severity Scales, Patient Global Impressions-Improvement scale, Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, Social and Occupational Functioning Assessment Scale and Quality of Life and Enjoyment Scale (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form). Generalised estimated equations examined the two-way interactions of personality disorder by time or treatment and investigated personality disorder as a non-specified predictor of outcomes. RESULTS: Over time, the Patient Global Impressions-Improvement scores were significantly higher in those in the personality disorder group. No other significant differences in the two-way interactions of personality disorder by treatment group or personality disorder by time were found. Personality disorder was a significant but non-specific predictor of poorer outcomes on the Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, regardless of time or treatment group. CONCLUSIONS: This study highlights the potential impact of maladaptive personality traits on treatment outcomes and suggests that the presence of comorbid personality disorder may confer additional burden and compromise treatment outcomes. This warrants further investigation as does the corroboration of these exploratory findings. This is important because understanding the impact of comorbid personality disorder on bipolar disorder may enable the development of effective psychological and pharmacotherapeutic options for personalised treatments.

The role of micrometastasis in high-risk skin cancers.

The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.

Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.

AIMS: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response. METHODS: This placebo-controlled, randomized, multicenter, parallel-group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17-item total score ≥ 14; historical inadequate response to 1-3 ADTs) with inadequate response to 8-week single-blind, prospective SSRI/SNRI treatment to 6-week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression-Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs). RESULTS: Of 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post-baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was -8.5 (0.47) with brexpiprazole 1 mg, -8.2 (0.47) with brexpiprazole 2 mg, and -6.7 (0.47) with placebo (placebo-adjusted LSM difference [95% CI]: 1 mg, -1.7 [-3.0, -0.4]; P = 0.0089; 2 mg, -1.4 [-2.7, -0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated. CONCLUSION: Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT.

Propolis as an adjunctive therapy for treatment of uncomplicated cystitis in women: A randomized double-blind placebo-controlled trial.

The current research is designed to investigate the effect of propolis supplementation on the clinical manifestations in women suffering from uncomplicated cystitis. In this randomized double-blind, placebo-controlled trial, 120 women with uncomplicated cystitis were selected and randomly assigned into two groups to receive two 500 mg capsules of propolis or placebo daily for 7 days along with ciprofloxacin (250 mg). Clinical symptoms including hematuria, urinary frequency, dysuria, suprapubic pain, and urgency, as well as bacteriuria, were assessed before and after the intervention. After supplementation, participants in the intervention group had significantly fewer days of urinary frequency (p < 0.001), dysuria (p = 0.005), and urgency (p = 0.03). However, there was no significant difference between the two groups regarding hematuria and suprapubic pain (p > 0.05). Furthermore, the severity of bacteriuria decreased significantly in both groups. In conclusion, it seems that propolis supplementation in women with uncomplicated cystitis could improve urinary frequency, dysuria, and urgency. However, further clinical trials should be conducted to fully understand the effects of propolis in women suffering from uncomplicated cystitis.

Non-surgical treatment of residual periodontal pockets using sodium hypochlorite/amino acid gel and cross-linked hyaluronic acid-a 9-month pilot randomized controlled clinical trial.

OBJECTIVES: This pilot randomized controlled clinical trial compares the clinical outcome obtained in persistent periodontal pockets during 9-month follow-up of supportive periodontal step 4 treatment performed by either combining subgingival instrumentation with adjunctively used sodium hypochlorite/amino acid gel and crosslinked hyaluronic acid (xHyA) or subgingival instrumentation alone. MATERIALS AND METHODS: Study protocol is registered under NCT06438354 at Clinicaltrials.gov. Patients seeking further therapy after completed step 2 non-surgical periodontal treatment underwent either repeated subgingival instrumentation with adjunctive application of sodium hypochlorite/amino acid gel and crosslinked hyaluronic acid (group A) or repeated subgingival instrumentation alone (group B). One calibrated investigator performed the treatment sequence in both groups accordingly. Subgingival instrumentation of the residual pockets was carried out under local anaesthesia using hand- and ultrasonic instruments, as well as air polishing in both groups. Patients were instructed to continue oral hygiene without any restriction. At 3-month re-evaluation treatment was repeated accordingly at sites with persistent 5 mm probing depth and BoP + . Clinical attachment level (CAL), pocket probing depth (PPD), gingival recession (GR), and bleeding on probing (BoP) were recorded at baseline (T1), 3- (T2) and 9-month (T3) post-op, with CAL as a primary outcome measure. RESULTS: In total 52 patients (20 females and 32 males, mean age 58.4 ± 2.4 years) presenting with 1448 sites which required further periodontal treatment were enrolled. Both groups exhibited homogeneity in terms of age, gender, smoking habit, initial number of sites, and BOP. At 9-month evaluation, PD reduction and CAL gain showed significant differences between the test and control group, favouring the adjunctive treatment. GR tended to exhibit more recovery in the test group compared to the control group. Although BOP frequency effectively reduced in both groups, there was no statistically significant difference between the two groups. CONCLUSION: Within the limits of the study, the present data indicates that, during subgingival instrumentation of persistent pockets, the adjunctive usage of sodium hypochlorite/amino acid gel and xHyA sufficiently improves the clinical outcomes. The continuous improvement of CAL in association with the GR scores observed in group A, indicates that sites subjected to adjunctive treatment may indicate a tendency for a regenerative response to treatment within the 9-month follow-up period.

Marginal resection and infracyanine green-mediated photodynamic therapy in the management of feline eyelid squamous cell carcinoma: Two cases.

OBJECTIVE: Describe the presenting features, surgical procedure, and clinical outcomes of two cats managed with marginal resection and photodynamic therapy (PDT) for eyelid squamous cell carcinoma (SCC). ANIMALS STUDIED: A 12-year-old female spayed domestic shorthair cat (case 1) and a 10-year-old female spayed domestic shorthair cat (case 2). PROCEDURES: Following marginal resection of the eyelid neoplasm, hemostasis was achieved using a handheld cautery unit then 1 mL of infracyanine green was injected into the surgical wound bed. Photodynamic therapy was performed using an 810 nm diode laser in two consecutive steps: (i) six cycles at 500 mW for 30 s per cycle, using a rapid movement; then (ii) one (case 1) or two cycles (case 2) of 30 s at 2000 mW, using a slow deliberate movement to effect (charred surface). RESULTS: Histopathology was consistent with SCC resected with incomplete margins in both cats. Follow-up duration was 416 and 161 days in case 1 and case 2, respectively. Consecutive exams and photo-documentation (in clinic or by owners) showed appropriate healing of the lower eyelid, with a smooth lid margin, and no evidence of tumor regrowth or ocular irritation. Subtle trichiasis was noted in case 1 on day 185, but not at the last follow-up. CONCLUSIONS AND CLINICAL RELEVANCE: Marginal resection followed by PDT may be a valid alternative to complete surgical resection of periocular SCC in cats. The procedure was easy to perform, post-operative recovery was uncomplicated, and neither cat developed recurrent disease during the follow-up period.

The Purinergic P2X7 Receptor as a Target for Adjunctive Treatment for Drug-Refractory Epilepsy.

Epilepsy is one of the most common neurological diseases worldwide. Anti-seizure medications (ASMs) with anticonvulsants remain the mainstay of epilepsy treatment. Currently used ASMs are, however, ineffective to suppress seizures in about one third of all patients. Moreover, ASMs show no significant impact on the pathogenic mechanisms involved in epilepsy development or disease progression and may cause serious side-effects, highlighting the need for the identification of new drug targets for a more causal therapy. Compelling evidence has demonstrated a role for purinergic signalling, including the nucleotide adenosine 5'-triphosphate (ATP) during the generation of seizures and epilepsy. Consequently, drugs targeting specific ATP-gated purinergic receptors have been suggested as promising treatment options for epilepsy including the cationic P2X7 receptor (P27XR). P2X7R protein levels have been shown to be increased in the brain of experimental models of epilepsy and in the resected brain tissue of patients with epilepsy. Animal studies have provided evidence that P2X7R blocking can reduce the severity of acute seizures and the epileptic phenotype. The current review will provide a brief summary of recent key findings on P2X7R signalling during seizures and epilepsy focusing on the potential clinical use of treatments based on the P2X7R as an adjunctive therapeutic strategy for drug-refractory seizures and epilepsy.

Lactic Acid Bacteria-Derived Postbiotics as Adjunctive Agents in Breast Cancer Treatment to Boost the Antineoplastic Effect of a Conventional Therapeutic Comprising Tamoxifen and a New Drug Candidate: An Aziridine-Hydrazide Hydrazone Derivative.

Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from L. plantarum and L. rhamnosus cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine-hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics' potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.

Effect of Preoperative Coronal Plane Alignment on Actual Versus Predicted Alignment Using Patient Specific Instrumentation in Total Ankle Replacement.

Alignment in total ankle replacement is important for success and implant survival. Recently there has been the introduction and adoption of patient specific instrumentation for implantation in total ankle replacement. Current literature does not evaluate the effect of preoperative deformity on accuracy of patient specific instrumentation. A retrospective radiographic analysis was performed on 97 consecutive patients receiving total ankle replacement with patient specific instrumentation to assess the accuracy and reproducibility of the instrumentation. Subgroup analysis evaluated the effect of preoperative deformity. All surgeries were performed by fellowship trained foot and ankle surgeons without industry ties to the implants used. Preoperative and postoperative films were compared to plans based on computerized tomography scans to assess how closely the plan would be implemented in patients. Overall postoperative coronal plane alignment was within 2° of predicted in 87.6% (85 patients). Similarly, overall postoperative sagittal plane alignment was within 2° of predicted in 88.7% (86 patients). Tibial implant size was accurately predicted in 81.4% (79 patients), and talus implant size was correct in 75.3% (73 patients). Patients with preoperative varus deformity had a higher difference between predicted and actual postoperative alignment compared to valgus deformity (1.1° compared to 0.3°, p = .02). A higher average procedure time was found in varus patients, and more adjunctive procedures were needed in patients with varus or valgus deformity, but these were not significant, p > .5. Surgeons can expect a high degree of accuracy when using patient specific instrumentation overall, but less accurate in varus deformity.

Comparative Evaluation of Effectiveness of Omega-3 Fatty Acids as an Adjunct to SRP with Conventional SRP: A Randomized Clinical Trial.

AIM: This study aims to compare the effectiveness of "omega-3 fatty acids" as an auxiliary to "scaling and root planing (SRP)" with traditional "scaling and root planing" in periodontal treatment in humans. MATERIALS AND METHODS: This study is a randomized control trial and was carried out over a period of 3 months (registered on 02/07/2023). Thirty patients were singled out according to the inclusion criteria, each having periodontitis (Stage II Grade B), and were arbitrarily distributed into two groups (control and test). The test group was treated with "scaling and root planing" along with the adjunctive application of "omega-3 fatty acids" while the control group was treated with "scaling and root planing" alone. Monthly follow-up was carried out over 90 days. Clinical parameters such as pocket probing depth (PPD), gingival index (GI), bleeding index (BI), and plaque index (PI) were measured respectively at baseline and 3 months. The data was recorded and statistically analyzed. RESULTS: The soft tissue architecture remained stable. The mean full mouth plaque index (FMPI) score was statistically significant (p < 0.001) when the control group was compared to the test group with a mean difference of 0.12 ± 0.02. The mean full mouth papillary bleeding index (FMPBI) score decreased at 3 months and was statistically significant compared to baseline with a mean difference of 0.24 ± 0.04 (p < 0.001). When the test group was compared with the control group, the FMGI was not significant (p = 0.02), with a mean difference of 0.16 ± 0.19. The PPD was not significant (p =1) when comparing both the groups, with a mean difference of 0 ± 0.66. Although the clinical parameters were statistically significant at 3 months when compared to baseline in both the groups, the FMGI and PPD were not significant. CONCLUSION: The combined action of using omega-3 fatty acid as an auxiliary to conventional scaling and root planing improved the periodontal parameters including both the soft and hard tissue outcomes. CLINICAL SIGNIFICANCE: The present study indicated that supplementary usage of omega-3 fatty acids is more beneficial for treating chronic and mild periodontitis than scaling and root planing alone. Omega-3 fatty acids can be used as energy for our cells, reduce the risk of blood clotting, maintain bone health, regulate metabolism, and reduce inflammation. Host modulatory therapy (HMT) with omega-3 fatty acids aims at reducing inflammation. With HMT as an adjunct, a better result of periodontal therapy was expected. It enhanced the positive effects on periodontal parameters and both the soft and hard tissue outcomes. How to cite this article: Salian S, Dhadse PV, Patil R, et al. Comparative Evaluation of Effectiveness of Omega-3 Fatty Acids as an Adjunct to SRP with Conventional SRP: A Randomized Clinical Trial. J Contemp Dent Pract 2024;25(5):440-444.

Masculinization of the Chest in Transmen with Large Breasts.

Background and Objectives Surgery to masculinize the chest is a frequently sought-after procedure by transmen who wish to conform their physical appearance to their gender identity. In our study, the outcomes of surgical masculinization comprising subcutaneous mastectomy through a modified elliptical incision, liposuction, reduced inert nipple-areola grafting, and quilting stitches were analyzed. Materials and Methods Thirty-two transmen with large breasts and hypertrophied nipples and areolae underwent the above-mentioned masculinizing procedure in this prospective cohort study. Our statistically validated institutional aesthetic outcome assessment score (IAOAS) was used to analyze the outcomes at the end of the follow-up period. Results The average period of follow-up was 24.5 months. The average final IAOAS was 23.1. The rate of complications was found to be associated with using breast binders. In all, 22 of 32 patients (68.75%) had an excellent outcome score, while 10 patients (31.25%) had a good outcome score ( p = 0.025). Conclusion Top surgery is crucial for transmasculine patients to achieve their desired gender identity as males. It is imperative that this procedure is performed to their complete satisfaction. Our single-staged comprehensive approach of subcutaneous mastectomy and liposuction with reduced inert nipple and areola grafts, which aids in a swift transition to a male role, is a prerequisite for bottom surgery at our institute.

Efficacy and safety/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy. METHODS: A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events. RESULTS: Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, n = 4375), amisulpride [1.99 (1.55-2.55)], sulpiride [1.50 (1.03-2.17)], and quetiapine [1.48 (1.23-1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, n = 8349), ziprasidone [1.80 (1.07-3.04)], risperidone [1.59 (1.19-2.14)], aripiprazole [1.54 (1.35-1.76)], brexpiprazole [1.41 (1.21-1.66)], cariprazine [1.27 (1.07-1.52)], and quetiapine [1.23 (1.08-1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior. CONCLUSION: Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.

Cost-effectiveness of cenobamate for focal seizures in people with drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to estimate the cost-effectiveness of add-on cenobamate in the UK when used to treat drug-resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively. METHODS: We estimated the cost per quality-adjusted life-year (QALY) for cenobamate compared to brivaracetam, eslicarbazepine, lacosamide, and perampanel in the UK National Health Service over a lifetime time horizon. We used a Markov cohort structure to determine response to treatment, using pooled data from three long-term studies of cenobamate. A network meta-analysis informed the likelihood of response to therapy with brivaracetam, eslicarbazepine, lacosamide, and perampanel relative to cenobamate. Once individuals discontinued treatment, they transitioned to subsequent treatment health states, including other antiseizure medicines, surgery, and vagus nerve stimulation. Costs included treatment, administration, routine monitoring, event management, and adverse events. Published evidence and expert opinion informed the likelihood of response to subsequent treatments, associated adverse events, and costs. Utility data were based on Short-Form six-dimension form utility. Discounting was applied at 3.5% per annum as per National Institute for Health and Care Excellence guidance. Uncertainty was explored through deterministic and probabilistic sensitivity analyses. RESULTS: In the base case, cenobamate led to cost savings of £51 967 (compared to brivaracetam), £21 080 (compared to eslicarbazepine), £33 619 (compared to lacosamide), and £28 296 (compared to perampanel) and increased QALYs of 1.047 (compared to brivaracetam), 0.598 (compared to eslicarbazepine), 0.776 (compared to lacosamide), and 0.703 (compared to perampanel) per individual over a lifetime time horizon. Cenobamate also dominated the four drugs across most sensitivity analyses. Differences were due to reduced seizure frequency with cenobamate relative to comparators. SIGNIFICANCE: Cenobamate improved QALYs and was less costly than brivaracetam, eslicarbazepine, lacosamide, and perampanel. Therefore, cenobamate may be considered as a cost-effective adjunctive antiseizure medication for people with drug-resistant focal seizures.