Side-Effects on the Renal function of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

Background: Acute kidney injury (AKI) is a frequent complication in patients undergo-ing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to a combination of several factors: increased intra-abdominal pressure, heat stress and drug tox-icity. Methods: Patients admitted to Intensive Care Unit after CRS and HIPEC during 129 months. Data recorded were: demographic characteristics; severity of illness, haematology and basic chemistry panels (renal function and electrolytes), type of cancer and extension, HIPEC drug and temperature, fluid balance, ICU and hospital stay and mortality. Results: 123 patients were included, only 4.9% developed AKI. AKI was more frequent on patients with ovarian cancer or in those who received doxorubicina as intraperitoneal chemotherapy; also, among those who had higher positive fluid balance during surgery, had higher SOFA or were under mechanical ventilation at ICU admission. There were not differences in mortality according to the development of AKI. Electrolyte disorders appeared in 95.8% of the patients, mainly hypocalcemia and hypokalemia. Conclusion: In our study, the incidence of AKI has been low. The presence of hydroelectrolytic alterations and polyuria was very frequent. The type of cancer, no mitomycin-based regimens and positive fluid balance during surgery were factors that suggest increased risk of AKI. However, although patients with AKI were clinically worse it was not associated with higher mortality.

Updates in Systemic Treatment of Hormone Receptor-Positive Early-Stage Breast Cancer.

OPINION STATEMENT: Hormone-receptor positive (HR +) and human epidermal growth factor receptor 2 (HER2) negative early breast cancer (eBC) is a heterogeneous disease with several contributing factors for increased risk of recurrence, including tumor features, individual biomarkers, and genomic risk. The current standard approach in the management of HR + /HER2neg eBC includes chemotherapy and endocrine therapy (ET), and additional therapies based on risk profile, menopausal status, and genetics are sometimes appropriate. The risk of recurrence is more pronounced in patients with high-risk eBC including large tumor size, nodal involvement, high proliferative index, and genetic predisposition. In premenopausal patients with high-risk eBC, ovarian function suppression in combination with adjuvant ET improves survival. In postmenopausal patients, extended aromatase inhibitor (AI) therapy can be considered. Recent trials have identified novel treatment approaches to reduce the risk of recurrence in high-risk HR + /HER2neg eBC including the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to adjuvant ET. For patients with germline BRCA1/BRCA2 mutations, adjuvant poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been shown to improve overall survival (OS). However, despite these recent advances, the risk of recurrence remains substantial, highlighting an area of unmet need. There are several ongoing clinical trials further investigating the role of CDK 4/6 inhibitors and immunotherapy in high-risk HR + /HER2neg eBC.

Risk factors for postoperative complications in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: A meta-analysis and systematic review.

OBJECTIVE: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is one of the most effective treatments for intraperitoneal malignancies. However, current research on risk factors for postoperative complications needs to be more consistent. This study aimed to conduct a meta-analysis of the risk factors for postoperative complications in CRS + HIPEC patients. METHODS: Studies meeting the inclusion criteria were screened by searching the Embase, PubMed, Cochrane and Web of Science databases. RevMan and STATA software were used to analyze the data extracted from the included articles. RESULTS: A total of 15 articles with 4021 patients were included in the meta-analysis. The results revealed that sex, elevated peritoneal cancer index, prolonged duration of surgery and smoking habits were risk factors for postoperative complications in CRS + HIPEC patients. In contrast, BMI, eGFR, age, history of preoperative chemotherapy, history of preoperative surgery, and history of neoadjuvant therapy had no significant effect on postoperative complications in the CRS + HIPEC group. The effects of diabetes, hypertension, preoperative albumin level, tumor location and chemotherapy regimen on the occurrence of complications need to be further investigated. CONCLUSIONS: We identified several risk factors for postoperative complications after CRS + HIPEC, which should help clinicians minimize the incidence of postoperative complications and make more beneficial decisions for cancer patients who need treatment.

A Comparison of Traditional Chinese Medicine and Multiple Conventional Therapy in Treating Oral Lichen Planus: A Network Meta-analysis.

PURPOSE: To evaluate and compare the efficacy of seven conventional treatments and traditional Chinese medicine (TCM) combined therapies for oral lichen planus. MATERIALS AND METHODS: This study employs PubMed, Web of Science, Cochrane Library, and Cnki to collect studies. After evaluating the quality and bias risk, RevMan 5.4.1 and R Gemtc package was utilised with a visual analogue scale and side effects as outcomes, to compare the efficacy of the seven treatments. RESULTS: This study included 20 studies, with a sample size of 1669. Our results suggest that photodynamic therapy and TCM demonstrate the most significant decrease in visual analogue scale and the rank is as follows: photodynamic therapy > TCM > TCM combined with non-hormonal immunosuppressive drugs > TCM combined with glucocorticoids > chloroquine combined with glucocorticoids > non-hormonal immunosuppressive drugs > glucocorticoids. Among them, compared to glucocorticoids, photodynamic therapy (-1.55, 95% CI: (-3.09, -0.02)), TCM (-1.25, 95% CI: (-2.46, -0.06)) significantly outperform in statistics. Moreover, no side effects were reported by the photodynamic therapy treatment. In the comparison with non-hormonal immunosuppressive drugs, the result indicates TCM (-4.17, 95% CI (-8.24, -0.34)), glucocorticoids (-2.78, 95% CI (-5.69, -0.17)) and their combination (-2.83, 95% CI (-5.93, -0.05)) have a significantly lower probability of the appearance of side effects. CONCLUSION: This study indicates that TCM, from the perspectives of efficacy and the likelihood of side effects, outperforms all other common therapies, besides photodynamic therapy, in treating oral lichen planus.

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Safety and efficacy of a picosecond 755-nm alexandrite laser combined with topical tranexamic acid in the treatment of melasma.

BACKGROUND: The picosecond 755-nm alexandrite laser and topical tranexamic acid (TA) have shown promise in treating melasma. AIM: This aim of this study was to evaluate the efficacy and safety of combining to a picosecond 755-nm alexandrite laser combined with topical TA for melasma treatment. PATIENTS AND METHODS: Forty-eight patients' facial halves with bilateral symmetrical melasma were randomized to receive either topical TA and picosecond laser treatment or laser monotherapy. All patients received three consecutive picosecond laser treatment sessions at 4-week intervals, and additional one side facial received topical TA treatment twice daily until 4 weeks after the third treatments. Efficacy was assessed using the Modified Melasma Area and Severity Index (mMASI) score, VISIA (Canfield, USA) red area feature counts, and average pore volume as measured by Antera 3D®. Patient satisfaction was evaluated through questionnaires. RESULTS: Thirty-five patients completed the study. Post-treatment, mMASI scores and VISIA red area feature counts were lower in combination therapy halves and laser monotherapy halves, and average melanin level was lower in the combination therapy halves (p < 0.05). Comparisons between the combination therapy halves and laser monotherapy halves after the third treatment revealed significant differences in mMASI scores, melanin levels, and VISIA red area feature counts (p < 0.05). After treatment, patient satisfaction rates in the combination therapy halves and monotherapy halves was 71.4% and 54.3%, respectively (p < 0.05). No obvious adverse effects were observed in the combination therapy halves; whereas, 10.42% (5/48) of participants in the laser monotherapy halves experienced temporary pigmentation, which resolved within 3 months. CONCLUSION: The picosecond 755-nm alexandrite laser, when used independently and in combination with topical TA, has been proven to be effective in the improvement of melasma. However, the combined treatment approach showed a more pronounced improvement in melasma symptoms, with higher patient satisfaction, and was associated with a lower incidence of adverse effects. These findings strongly support that integrating topical TA with picosecond laser therapy as a superior therapeutic strategy for melasma management. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200057771.

Efficacy and safety of ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma: A meta-analysis.

OBJECTIVE: Meta-analysis was used to assess the efficacy and safety of ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma. METHODS: Randomized controlled studies on ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma were searched in the databases of PubMed, Embase, Cochrane library, web of science with a search deadline of March 14, 2024. Data were analyzed using Stata 15.0. RESULT: Six randomized controlled studies involving 520 individuals were finally included, the results of meta-analysis showed that ultrasound-guided radiofrequency ablation combined with TACE can improve objective response rate [RR = 1.52, 95%CI (1.28, 1.81)], improve disease control rate [RR = 1.15, 95%CI (1.06, 1.24)], The survival rate [RR = 1.34, 95%CI (1.19,1.51)] did not increase adverse reactions [RR = 1.34, 95%CI (1.00,1.79)]. CONCLUSION: Based on the findings of the current study, ultrasound-guided radiofrequency ablation combined with TACE was found to improve the objective remission rate, disease control rate, and did not increase adverse events in patients with hepatocellular carcinoma.

Efficacy and safety of transarterial chemoembolization plus lenvatinib combined with PD-1 inhibitors versus transarterial chemoembolization plus lenvatinib for unresectable hepatocellular carcinoma: a meta-analysis.

Background: Locoregional treatment combined with systemic therapy is expected to play a synergistic anticancer role. We conducted this systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without programmed cell death protein-1 (PD-1) inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC). Methods: From the inception date to April 2024, the data from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials. gov were used for meta-analysis. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were used to measure the pooled effect. Results: This study included 10 retrospective cohort studies, including 1128 patients. The OS (HR=0.51; 95% CI: 0.43-0.60, P < 0.05), PFS (HR=0.52; 95% CI: 0.45-0.61, P < 0.05), ORR (RR = 1.58; 95% CI: 1.37-1.83; P < 0.05) and DCR (RR = 1.31; 95% CI: 1.20-1.43; P < 0.05) were significantly higher in TLP group than in the TL group. The incidence of AEs was acceptable. Prognostic factor analysis identified that ECOG PS (1/0), Child-Pugh class (B/A), BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for OS. BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for PFS. Conclusion: The TLP group had better efficacy for uHCC than that of the TL group, with acceptable safety. Systematic review registration: PROSPERO, identifier (CRD42023420093).

Efficacy of sorafenib plus transcatheter arterial chemoembolization in treating hepatocellular carcinoma with portal vein tumor thrombosis: A meta-analysis.

This meta-analysis aimed to evaluate the efficacy of sorafenib plus transcatheter arterial chemoembolization (TACE) in treating hepato-cellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Twelve randomized controlled trials published until 28th Sep 2022 were finally included. Of the total 1746 patients, of whom 458 received sorafenib and TACE treatment (Group S+TACE), and 1288 only underwent TACE (Group TACE), were enrolled. Outcomes including time to progression (TTP), objective response rate (ORR), disease control rate (DCR), overall survival (OS), survival rate (SR), and adverse reactions, were extracted. The OS (HR: 0.596, 95 %CI: 0.507-0.685, p < 0.001; I2 = 0.0 %) and TTP (HR: 0.379, 95 %CI: 0.205-0.553, p < 0.001; I2 = 4.5 %) in the S+TACE group were longer than those in the TACE group. The ORR (RR: 2.101, 95 %CI: 1.555-2.839, p < 0.001; I2 = 0.0 %), DCR (RR: 1.547, 95 %CI: 1.126-2.126, p = 0.007; I2 = 79.6 %) and SR (RR: 1.416, 95 %CI: 1.183-1.694, p < 0.001; I2 = 83.8 %) in the S+TACE group were higher than those in the TACE group. Compared with the TCAE group, the higher odds of HFSR, oral ulcer, and diarrhea among patients with HCC complicated by PVTT were discovered in the S+TACE group. The marginal significance was found in ascites and gastrointestinal bleeding between the two groups. Sorafenib plus TACE has good efficacy and mild adverse reactions, which may be worthy of clinical promotion.

Clinical efficacy and safety of acupuncture combined with statin in dyslipidemia: A meta-analysis and system review.

BACKGROUND: This study aims to systematically evaluate the clinical efficacy and safety of acupuncture in combination with statin therapy compared to statin monotherapy for the treatment of dyslipidemia. METHODS: A comprehensive search for relevant randomized controlled trials assessing the clinical efficacy of acupuncture and statin combination in the treatment of dyslipidemia was conducted. Databases including PubMed, EMbase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang database, and China Science and Technology Journal Database were searched up to October 27, 2023. RESULTS: Sixteen Chinese-language studies involving a total of 1333 subjects were included for analysis. The meta-analysis revealed that the total effective rate of acupuncture combined with statin was significantly higher than that of statin alone (odds ratios = 3.32, 95% confidence intervals [CI] = 2.33 to 4.72). Furthermore, the combination of acupuncture with statin treatment resulted in a significant reduction in triglyceride levels (mean differences [MD] = -0.72 mmol/L, 95% CI = -1.05 to -0.4), total cholesterol levels (MD = -0.79 mmol/L, 95% CI = -1.07 to -0.51), low-density lipoprotein cholesterol levels (MD = -0.61 mmol/L, 95% CI = -0.95 to -0.27) and traditional Chinese medicine syndrome integral (MD = -1.32, 95% CI = -1.75 to -0.89), compared to statin treatment alone. Additionally, the high-density lipoprotein cholesterol level was higher in the combined acupuncture and statin treatment group than in the statin treatment alone group (MD = 0.44 mmol/L, 95% CI = 0.09 to 0.79). Notably, the rate of adverse reactions reported with combined acupuncture and statin treatment was lower than that with statin therapy alone. CONCLUSION: Our findings support the potential of acupuncture combined with statin as a viable clinical treatment option for dyslipidemia. However, it is important to note that current research on the mechanism of acupuncture for lipid-lowering has not yielded definitive results, and there are inherent biases in the conducted clinical studies.

Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases.

BACKGROUND: Psychedelic-assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic-assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life-threatening diseases (e.g. cancer). However, these substances are illegal in most countries and have been associated with potential risks. OBJECTIVES: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators (e.g. antidepressants) for treatment of anxiety, depression, and existential distress in people with life-threatening diseases. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers on 30 March 2024. In addition, we undertook reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with no restrictions regarding comorbidity, sex, or ethnicity. Interventions comprised a substance-induced psychedelic experience preceded by preparatory therapeutic sessions and followed by integrative therapeutic sessions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies in the review, which evaluated two different interventions: psychedelic-assisted therapy with classical psychedelics (psilocybin ('magic mushrooms') and lysergic acid diethylamide (LSD)), and psychedelic-assisted therapy with 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'). The studies randomised 149 participants with life-threatening diseases and analysed data for 140 of them. The age range of participants was 36 to 64 years. The studies lasted between 6 and 12 months, and were conducted in outpatient settings in the USA and in Switzerland. Drug companies were not involved in study funding, but funding was provided by organisations that promote psychedelic-assisted therapy. Primary outcomes (at 1 to 12 weeks) Anxiety Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in anxiety when compared to active placebo (or low-dose psychedelic): State Trait Anxiety Inventory (STAI-Trait, scale 20 to 80) mean difference (MD) -8.41, 95% CI -12.92 to -3.89; STAI-State (scale 20 to 80) MD -9.04, 95% CI -13.87 to -4.21; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on anxiety, compared to placebo, is very uncertain: STAI-T MD -14.70, 95% CI -29.45 to 0.05; STAI-S MD -16.10, 95% CI -33.03 to 0.83; 1 study, 18 participants; very low certainty evidence. Depression Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in depression when compared to active placebo (or low-dose psychedelic): Beck Depression Inventory (BDI, scale 0 to 63) MD -4.92, 95% CI -8.97 to -0.87; 4 studies, 112 participants; standardised mean difference (SMD) -0.43, 95% CI -0.79 to -0.06; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on depression, compared to placebo, is very uncertain: BDI-II (scale: 0 to 63) MD -6.30, 95% CI -16.93 to 4.33; 1 study, 18 participants; very low certainty evidence. Existential distress Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) compared to active placebo (or low-dose psychedelic) may result in a reduction in demoralisation, one of the most common measures of existential distress, but the evidence is very uncertain (Demoralisation Scale, 1 study, 28 participants): post treatment scores, placebo group 39.6 (SEM 3.4), psilocybin group 18.8 (3.6), P ≤ 0.01). Evidence from other measures of existential distress was mixed. Existential distress was not measured in people receiving psychedelic-assisted therapy with MDMA. Secondary outcomes (at 1 to 12 weeks) Quality of life When classical psychedelics were used, one study had inconclusive results and two reported improved quality of life, but the evidence is very uncertain. MDMA did not improve quality of life measures, but the evidence is also very uncertain. Spirituality Participants receiving psychedelic-assisted therapy with classical psychedelics rated their experience as being spiritually significant (2 studies), but the evidence is very uncertain. Spirituality was not assessed in participants receiving MDMA. Adverse events No treatment-related serious adverse events or adverse events grade 3/4 were reported. Common minor to moderate adverse events for classical psychedelics were elevated blood pressure, nausea, anxiety, emotional distress, and psychotic-like symptoms (e.g. pseudo-hallucination where the participant is aware they are hallucinating); for MDMA, common minor to moderate adverse events were anxiety, dry mouth, jaw clenching, and headaches. Symptoms subsided when drug effects wore off or up to one week later. Certainty of the evidence Although all six studies had intended to blind participants, personnel, and assessors, blinding could not be achieved as this is very difficult in studies investigating psychedelics. Using GRADE criteria, we judged the certainty of evidence to be low to very low, mainly due to high risk of bias and imprecision (small sample size). AUTHORS' CONCLUSIONS: Implications for practice Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life-threatening disease. Psychedelic-assisted therapy seemed to be well tolerated, with no treatment-emergent serious adverse events reported in the studies included in this review. However, the certainty of evidence is low to very low, which means that we cannot be sure about these results, and they might be changed by future research. At the time of this review (2024), psychedelic drugs are illegal in many countries. Implications for research The risk of bias due to 'unblinding' (participants being aware of which intervention they are receiving) could be reduced by measuring expectation bias, checking blinding has been maintained before cross-over, and using active placebos. More studies with larger sample sizes are needed to reduce imprecision. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing.

Neuropathic Pain in Cancer: What Are the Current Guidelines?

OPINION STATEMENT: Neuropathic cancer pain is experienced by 30-40% of patients with cancer. It significantly reduces quality of life and overall wellbeing for patients living with and beyond cancer. The underlying mechanisms of neuropathic pain in patients with cancer are complex and involve direct tumour involvement, nerve compression or infiltration, chemotherapy and/or radiotherapy-induced nerve damage, or post-surgical complications. It is crucial for healthcare professionals to assess and manage neuropathic cancer pain effectively. There is increasing recognition that standardisation of neuropathic pain assessment leads to tailored management and improved patient outcomes. Pain management strategies, including medication, interventional analgesia, physical and complementary therapy, can help alleviate neuropathic pain and improve the patient's comfort and quality of life.

Targeted RT study: results on early toxicity of targeted therapies and radiotherapy.

PURPOSE/OBJECTIVE: Currently, there are few prospective data on the tolerability of combining targeted therapies (TT) with radiation therapy (RT). The objective of this prospective study was to assess the feasibility and toxicity of pairing RT with concurrent TT in cancer patients. The aim was to enhance the existing evidence base for the simultaneous administration of targeted substances together with radiotherapy. METHODS: Prospective study enrollment was conducted at a single institution between March 1, 2020, and December 31, 2021, for all patients diagnosed with histologically confirmed cancer who underwent external beam radiotherapy in combination with targeted therapy. The study, known as the "targeted RT study," was registered in the German Clinical Trials Register under DRKS00026193. Systematic documentation of the toxicity profiles of different targeted therapies was performed, and the assessment of acute toxicity followed the guidelines of the National Cancer Institute Common Terminology Criteria for Adverse Events Version v5.0. RESULTS: A total of 334 patients underwent 683 radiation therapy series. During the course of RT, 51 different TT substances were concurrently administered. External beam radiotherapy was employed for various anatomical sites. The combination of RT and concurrent TT administration was generally well tolerated, with no instances of severe acute toxicity observed. The most commonly reported toxicity was fatigue, ranging from mild to moderate Common Terminology Criteria for Adverse Events (CTCAE) °I-°III. Other frequently observed toxicities included dermatitis, dyspnea, dysphagia, and dry cough. No toxicity greater than moderate severity was recorded at any point. In only 32 patients (4.7% of evaluated RT series), the concurrent substance administration was discontinued due to side effects. However, these side effects did not exceed mild severity according to CTCAE, suggesting that discontinuation was a precautionary measure. Only one patient receiving Imatinib treatment experienced a severe CTCAE °III side effect, leading to discontinuation of the concurrent substance due to the sudden occurrence of melaena during RT. CONCLUSION: In conclusion, the current study did not demonstrate a significant increase or additional toxicity when combining radiotherapy and concurrent targeted therapy. However, additional research is required to explore the specific toxicity profiles of the various substances that can be utilized in this context. TRIAL REGISTRATION NUMBER: DRKS00026193. Date of registration 12/27/2022 (retrospectively registered).

Neoadjuvant Therapy: Current Landscape and Future Horizons for ER-Positive/HER2-Negative and Triple-Negative Early Breast Cancer.

OPINION STATEMENT: Navigating the complex landscape of breast cancer treatment involves distinct strategies for luminal and triple-negative subtypes. While neoadjuvant chemotherapy historically dominates the approach for aggressive triple-negative tumors, recent evidence highlights the transformative impact of immunotherapy, alongside chemotherapy, in reshaping treatment paradigms. In luminal cancers, endocrine therapy, notably aromatase inhibitors, demonstrates promising outcomes in postmenopausal patients with low-grade luminal A tumors. However, integrating targeted therapies like CDK4/6 inhibitors in neoadjuvant setting remains inconclusive. Identifying predictive factors for treatment response, especially in luminal tumors, poses a challenge, emphasizing the necessity for ongoing research. A multidisciplinary approach, tailored to individual patient profiles, is crucial for maximizing efficacy while minimizing toxicity. As we strive to optimize breast cancer management, a comprehensive understanding of the distinct characteristics and treatment implications of luminal and triple-negative subtypes, including the transformative role of immunotherapy, is essential for informed decision-making and personalized care.

Efficacy, safety, tolerability and treatment durability of microneedling plus topical tranexamic acid in combination with topical modified Kligman lightening formula for melasma: A four-arm assessor and analyst blinded randomized controlled clinical trial.

BACKGROUND: The challenging management of melasma highlights the inadequacies of conventional therapies and their high risk of recurrence. Integrating microneedling for device-assisted drug delivery with tranexamic acid (TA), recognized for its melanin synthesis inhibition, presents a novel approach that warrants further investigation to fully assess its potential in enhancing melasma treatment efficacy. METHODS: Fifty moderate to severe melasma patients participated in this randomized outcome-assessor-blinded controlled trial. Patients were randomly allocated into two main groups. Group A received a modified Kligman formula on one hemi-face on alternate nights for 2 months (A1) and three sessions of microneedling with 10% topical TA on the other hemi-face at 1-month intervals (A2). Group B used the same modified Kligman formula on both sides of the face, with one side additionally receiving three sessions of microneedling with 4% TA (B1) and the opposite side with 10% TA (B2). Primary outcomes were % Modified Melasma Area and Severity Index (mMASI) and % visual analogue scale (VAS) change during 6 month follow-up. Adverse events including post-inflammatory hyperpigmentation (PIH) and treatment tolerability were recorded. RESULTS: Compared to baseline, the mean mMASI reduction immediately after the final session was higher in A1, B1, and B2 (56.84%, 50.88%, and 55.87%, respectively) than in A2, which saw only a 13.16% reduction. Efficacy notably declined after the cessation of treatment across all groups. While the efficacy within groups A1, B1, and B2 was comparable, microneedling with 4% or 10% TA combined with the topical modified Kligman formula proved more potent in patients at a lower risk of PIH. Overall, 22% of patients reported PIH, particularly in the A2 group (28% of hemi-faces), with its occurrence significantly associated with treatment during warmer seasons and in darker skin phototypes. Other adverse events were not observed in any patient. Patient satisfaction was highest in groups B1 and B2, where approximately 72% reported 'excellent' satisfaction. The lowest durability rate (16%) was observed in group A2, while the highest (72%) was seen in group B2, comparable with groups A1 and B1. Treatment tolerability was reported 100% in all groups. CONCLUSION: It was found that the modified Kligman formula outperformed microneedling-TA alone. However, with optimal patient selection, particularly targeting those at lower risk for PIH with lighter skin phototypes and scheduling treatments during less-sunny seasons, combining microneedling with 4% or 10% TA and the modified Kligman formula significantly enhanced efficacy and satisfaction rates compared to conventional topical treatment.

Modern Management of Gastric Neuroendocrine Neoplasms.

OPINION STATEMENT: Gastric neuroendocrine neoplasms (G-NENs) are a heterogeneous group of tumors that broadly fall into two groups. The first group, driven by oversecretion of gastrin, are generally multifocal, small, and behave indolently with a low (but non-zero) risk of progression and metastatic spread. They are conventionally categorized into type 1, with endogenous gastric-based overproduction of gastrin, and type 2 G-NEN, with overproduction of gastrin from an extra-gastric gastrin-secreting tumor. The second group, termed type 3 G-NEN, occur spontaneously and are potentially more aggressive, having a clinical course analogous to other neuroendocrine tumors of the gastrointestinal tract. Type 1 G-NEN can be managed with endoscopic surveillance and resection of visible lesions with great success, reserving surgery for the rare high-risk lesion, whereas surgical resection of the causative gastrin-secreting tumor in type 2 G-NEN is usually curative. Type 3 G-NEN is usually managed with formal surgical resection but there is growing evidence that limited surgery or even endoscopic resection in appropriately selected patients with low risk is both safe and effective. A novel subtype of G-NEN, associated with long-term proton pump inhibitor usage, is increasing in incidence. The pathophysiology seems to parallel type 1 G-NEN. In the setting of metastatic disease, which can occur in any subtype but is most common by far in type 3 G-NEN, the lack of trial data unique to G-NEN results in extrapolation of strategies and agents for treatment of non-gastric neuroendocrine disease. The rapid pace of development in this area is likely to benefit the metastatic G-NEN patient as well. As treatment is predicate on type of G-NEN, establishing the etiology of the lesion is crucial but growing knowledge of G-NEN pathophysiology and close collaboration between pathologists, gastroenterologists, radiologists, surgeons, and oncologists have enabled a growing trend towards de-escalation and less-invasive treatment paradigms.

Evolution of Treatment Strategies for Gestational Trophoblastic Neoplasia: Chemotherapy, Immunotherapy, and Molecular Targeted Therapy.

OPINION STATEMENT: In addressing Gestational Trophoblastic Neoplasia (GTN), it is imperative to acknowledge the evolving landscape of treatment options, especially in light of the challenges posed by traditional methods. While historically, surgical interventions, radiation therapy, and chemotherapeutic agents have been the mainstays, the emergence of resistance and high-risk scenarios necessitates a reevaluation of our therapeutic approaches. Our review highlights the promising advancements in immunotherapy and molecular targeted therapy as viable alternatives for GTN management. The introduction of immune checkpoint inhibitors and kinase inhibitors offers a paradigm shift, particularly for patients resistant to conventional chemotherapy regimens. These novel therapies not only exhibit efficacy but also demonstrate manageable toxicity profiles, particularly in high-risk cases. However, integrating these innovative treatments into established international guidelines presents a formidable task. As we move forward, it is imperative that future research not only prioritizes fertility preservation but also rigorously evaluates long-term toxicity implications. International collaboration becomes pivotal in addressing the nuances of this rare and complex disease. In conclusion, our review underscores the need for a nuanced approach to GTN treatment, one that prioritizes reduced toxicity and improved quality of life. By embracing the advancements in immunotherapy and molecular targeted therapy, we can pave the way for more effective and patient-centered care in the management of GTN.

A two-center randomized controlled trial of a repairing mask as an adjunctive treatment for mild to moderate rosacea.

OBJECTIVE: To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea. METHODS: Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score. RESULTS: A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants. CONCLUSION: The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use.

Combined low-dose isotretinoin and long-pulsed nd: YAG laser in the treatment of post-acne erythema.

Post-acne erythema (PAE) is a bothering skin condition that emerges from inflammatory acne and persists after its resolution. It is characterized by telangiectasia and erythematous macules. the role of 1064-nm Nd: YAG when combined with low-dose isotretinoin in the acne erythema treatment. forty-eight PAE patients were involved in the study. They were divided into two groups; group (A) patients administering a low dose of oral isotretinoin (10 mg/day) and underwent a total of six two-week interval sessions of 1064 ND-YAG laser treatment, group (B) patients administering a low dose of oral isotretinoin (10 mg/day) only. All adverse effects experienced during the course of therapy were documented, and photos were taken before the start of the treatment and following the end of the treatment duration. Following the completion of the therapeutic intervention, a significant improvement in clinical condition was observed in both groups, with more improvement in group (A) compared to group (B) as evidenced by a notable improvement in the score on the Clinician Erythema Assessment Scale (CEAS) and also a significant decrease in the mean value of optical density of the erythema. combined 1064-nm Nd: YAG with low-dose isotretinoin may be an efficient and secure line in the PAE treatment. Also, the combined therapy had superior results when compared to low-dose isotretinoin alone.

Neoadjuvant Immunotherapy in Non-melanoma Skin Cancers of the Head and Neck.

OPINION STATEMENT: Neoadjuvant immunotherapy will change the standard of care for advanced resectable cutaneous squamous cell carcinoma (cSCC) and possibly other non-melanoma skin cancers. With pathological complete response rates around 50% for cSCC in early studies, neoadjuvant therapy allows patients the possibility of significant reduction in tumor size, de-escalation of adjuvant therapy, and improved long-term outcomes. Patients must be carefully selected to ensure that there is a margin of safety with respect to resectability, such that if a tumor progresses on neoadjuvant therapy, there remains a curative surgical option that is acceptable to the patient. The optimal treatment paradigm is an area of active research, with many researchers questioning whether adjuvant therapy, or even local therapy, is necessary in patients who seem to have a complete response. The ability to predict who will respond will become even more critical to answer, as a significant number of patients do not want to risk their disease progressing, especially in cosmetically sensitive areas of the head and neck. Recent studies in melanoma show promise for improved response rates using combination therapies, and these strategies may apply to cSCC as well. The use of LAG-3 inhibitors or mRNA vaccine technology may further improve the utility of neoadjuvant strategies.