Introduction: Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic melanoma; however, predictive markers of therapeutic response remain poorly defined. This study systematically assesses clinical, histological, and molecular predictors associated with survival outcomes in melanoma patients treated with ICIs. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, a systematic search was conducted in MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published between January 2018 and October 2025. Eligible studies reported associations between predictive factors and overall survival (OS) or progression-free survival (PFS) in adult melanoma patients receiving ICIs. Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) from univariate (UVA) and multivariate analyses (MVA) were synthesized using random-effects meta-analyses. Results: Sex was not a consistent predictor (contradictory effects; PFS heterogeneity I2 ≈ 90%), whereas older age predicted worse OS (MVA continuous: HR 1.05, 95% CI 1.02-1.08; UVA ≥ 65 vs. <65: HR 1.70, 95% CI 1.36-2.12). Poor performance status, assessed using the Eastern Cooperative Oncology Group (ECOG) scale, strongly predicted inferior outcomes (ECOG ≥ 1 vs. 0: MVA OS HR 2.01, 95% CI 1.61-2.51; MVA PFS HR 1.49, 95% CI 1.18-1.88; ECOG ≥ 2 vs. <2: MVA OS HR 2.24, 95% CI 1.79-2.81). Elevated lactate dehydrogenase (LDH) was consistently associated with poorer survival (MVA OS HR 1.71, 95% CI 1.53-1.91; MVA PFS HR 1.61, 95% CI 1.41-1.85), whereas body mass index (BMI) > 25 kg/m2 was associated with improved OS (HR 0.82, 95% CI 0.68-0.98). Higher disease burden predicted worse prognosis (Stage IV vs. III: MVA OS HR 1.57, 95% CI 1.16-2.13; >2 metastatic sites vs. ≤2: MVA OS HR 2.38, 95% CI 1.40-4.07; brain metastases: MVA OS HR 1.69, 95% CI 1.30-2.20; MVA PFS HR 1.52, 95% CI 1.00-2.33). Histologic and molecular factors showed prognostic value: ulceration worsened OS (UVA HR 2.08, 95% CI 1.25-3.44) and PFS (UVA HR 2.97, 95% CI 1.39-6.32); acral subtype had poorer OS than cutaneous melanoma (MVA HR 2.99, 95% CI 1.63-5.48); high tumor mutational burden (TMB) improved PFS (UVA HR 0.47, 95% CI 0.33-0.70); and cutaneous immune-related adverse events (irAEs) were associated with favorable outcomes (skin disorders: UVA OS HR 0.26, 95% CI 0.14-0.47; UVA PFS HR 0.50, 95% CI 0.34-0.74). In contrast, detectable circulating tumor DNA (ctDNA) predicted markedly worse PFS (MVA HR 4.72, 95% CI 2.31-9.65) and a non-significant trend toward worse OS (MVA HR 3.34, 95% CI 0.96-11.67). Liver metastases and programmed death-ligand 1 (PD-L1) expression were not significantly associated with survival. Discussion: This meta-analysis synthesizes evidence on clinicopathologic, laboratory, and histopathologic predictors of immunotherapy outcomes in metastatic melanoma. Performance status, age, LDH, BMI, and metastatic burden consistently correlated with prognosis, while ulceration, disease stage, and TMB emerged as key histologic determinants. Conversely, PD-L1 and gender showed no consistent predictive value, whereas cutaneous immune-related adverse events and ctDNA reflected favorable and poor outcomes, respectively. These findings highlight the multifactorial nature of immunotherapy response and support the further development of integrated prognostic models to refine patient stratification and optimize treatment outcomes.

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Background:Over recent years, dermoscopy has proven useful not only for diagnosing skin conditions but also as a tool for predicting treatment response in inflammatory dermatoses. However, no data are available on dermoscopic predictors in papulopustular rosacea (PPR). Objective:To evaluate whether certain clinical and dermoscopic findings serve as positive or negative predictors of response to topical ivermectin or metronidazole in PPR. Methods:Twenty-three patients with moderate-to-severe PPR were enrolled. Ten patients received ivermectin 10 mg/g cream and 13 received metronidazole 1% gel (non-randomized, based on physician preference), applied once daily for 8 weeks. Inflammatory lesion counts and key clinical/dermoscopic features were assessed at baseline and after 8 weeks by two independent, blinded physicians. Post-treatment clinical outcomes (optimal response: >75% lesion reduction; partial response: 50-75% reduction) were correlated with baseline features. Results:Both treatments significantly reduced inflammatory lesion counts (p<0.001 for both). Any response (optimal or partial) occurred in 7/10 (70%) ivermectin-treated and 8/13 (62%) metronidazole-treated patients. Optimal response occurred in 5/10 (50%) ivermectin-treated and 4/13 (31%) metronidazole-treated patients. In the ivermectin group, all patients who achieved optimal response had baseline protruding follicular plugs (PFPs) (5/5, 100%) in dermoscopy, which are indicators of demodex tails. Those with partial or minimal/no response in the ivermectin group did not have baseline PFPs (0/5). Baseline PFPs were significantly associated with optimal response to ivermectin (p=0.004). In the metronidazole group, all 4 optimal responders did not have baseline PFPs. All the 4 patients in the metronidazole group with baseline PFPs showed minimal/no response, though this was not statistically significant (p=0.176). No other baseline features significantly predicted response in either treatment group. Conclusion:PFPs in dermoscopy of moderate-to-severe PPR serve as positive predictors for optimal response to topical ivermectin, but not metronidazole. This observation warrants validation in larger controlled trials.

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication of antiresorptive and antiangiogenic drugs with no consensus on optimal treatment. This study aimed to evaluate the clinical outcomes of MRONJ patients managed at a tertiary referral center over a 15-year period. Methods: We conducted a retrospective cohort study of 130 patients diagnosed with MRONJ (per AAOMS criteria) at a single tertiary hospital between 2006 and 2021. Data on demographics, underlying disease, drug history, MRONJ stage, triggering events, and treatment (conservative vs. surgical) were collected from medical records. Treatment outcomes were categorized as complete resolution, stable disease, or progression. Univariate and multivariate logistic regression analyses were performed to identify predictors of resolution. Results: Most patients (84.6%) had an underlying malignancy. The primary causative agents were zoledronic acid (47.7%) and denosumab (30.0%), the most frequent site was the mandible (66.2%), and the main trigger was dental extraction (59.2%). Crude resolution rates were 20.3% for conservative management versus 83.6% for surgical management. Treatment was stage-driven, with surgery common in advanced stages. At 12 months, 43.1% of all patients achieved complete resolution, and 52.3% remained stable. Multivariate analysis confirmed surgical treatment as the only independent predictor of complete resolution (OR = 20.1, 95% CI: 8.1–50). Conclusions: In this cohort, conservative care was generally sufficient for Stage I disease, while surgical intervention was the strongest predictor of healing and provided reliable outcomes for advanced MRONJ. These findings support an individualized, stage-appropriate treatment strategy.

Background Despite durable responses achieved with Immune Checkpoint Inhibitors (ICIs), data about optimal duration of treatment, especially in the context of adverse events, remain scarce. Objective To systematically review the evidence concerning the impact of treatment discontinuation with ICIs for reasons other than progressive disease (PD) on relapse rates and survival of melanoma patients. Methods A systematic literature search was conducted in three electronic databases until July 2024. Studies referring to melanoma patients who ceased ICIs electively (i.e. due to complete response (CR), protocol completion or patient/physician's wish) or due to treatment-limiting toxicities (TLTs) were selected. Relapse rates (RRs) post cessation, time to PD, rechallenge and disease control rate (DCR) after 2nd course were the main outcomes. Random-effects models were preferred, and subgroup and sensitivity analyses were conducted to investigate possible sources of heterogeneity. Results 38 and 35 studies were included in qualitative and quantitative synthesis, respectively. From 2542 patients discontinued treatment with ICIs electively or due to TLTs, 495 experienced progression [number of studies (n)=34, RR 20.9%, 95%CI 17.1 - 24.7%, I2 85%) and higher rates were detected in patients with TLTs compared to elective discontinuation. Mean time to PD was 14.26 months (n=18, mean time 14.26, 95%CI 11.54 - 16.98, I2 93%) and was numerically higher in patients who ceased for CR compared to patients with TLTs. Treatment duration before cessation was not associated with risk and time to relapse, while mucosal melanomas and non-CR as BOR during treatment led to increased risk for relapse and shorter time to PD compared to other histologic subtypes or CR. Rechallenge with ICI resulted in 57.3% DCR and 28.6% pooled CR rates (n=22, CR rate 28.6%, 95%CI 17.1 - 40.2, I2 68%). Heterogeneity among studies was high, but subgroup analysis based on type of ICI used (anti-CTL4 and anti-PD1 inhibitor or anti-PD1 monotherapy) and type of study (RCTs or observational studies), along with sensitivity analyses did not reveal significant alterations in results. Conclusion Discontinuation of ICIs in patients without progression is possible. Outcomes to rechallenge with ICIs may differ depending on the reason for discontinuation, but remains a considerable option. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024547792.

Introduction Data about the role of dermatoscopy-based artificial intelligence (AI) models on melanoma prognosis remain scant. Methods A comprehensive literature search was conducted in electronic databases until June 2025. Studies referring to machine learning algorithms (MLAs) trained on dermatoscopic images and analyzing the risk of melanoma metastasis were included. Also, due to scarcity of data regarding direct metastasis prediction, studies assessing melanoma prognostic factors, including Breslow thickness (BT), ulceration and histopathological subtype were analyzed. Results 18 studies met the inclusion criteria. Two studies focused on metastasis prediction: a pre-trained ResNet50 demonstrated comparable accuracy to tumor prognostic factors, while a Foundation model achieved AUC 0.96 (95 %CI 0.93 – 0.99). 13 studies assessed MLAs for BT prediction, using clinically meaningful thresholds (0.8 or 2.0 mm). MLAs showed substantial accuracy in binary tasks, particularly when advanced models (i.e. semi-supervised learning), or sophisticated loss of function techniques were employed. However, the inherent complexity of multiclass tasks reduced performance, due to class imbalance and overlapping image features. Furthermore, despite explainable AI highlighted blue pigmentation and atypical vascular pattern indicative of thick melanomas, models’ performance constraints were also noticed. Across BT continuum, models struggled to classify correctly lesions with intermediate (0.4–1.1 mm) or very thick melanomas. Finally, 3 studies evaluated MLAs for histopathological subtype recognition, with transfer learning achieving high accuracy across superficial spreading, nodular and acral subtypes. Outcomes MLAs based on dermatoscopy demonstrated feasibility for predicting metastasis and prognostic factors of melanoma preoperatively. Future studies integrating this into multimodal frameworks, including digital pathology and gene signatures, seems important.

Background/Objectives: Accurate surgical margin delineation is essential in the treatment of non-melanoma skin cancers (NMSCs), particularly basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), to reduce recurrence and metastasis. Dermoscopy improves diagnostic accuracy for skin tumors, but its utility for preoperative margin assessment remains underexplored. To compare dermoscopy-guided versus clinical visual inspection for preoperative margin assessment in NMSC excision, focusing on histological clearance rates and surgical outcomes. Methods: This systematic review and meta-analysis followed PRISMA 2020 guidelines. MEDLINE, Cochrane CENTRAL, Scopus, and Web of Science were searched from inception to 1 July 2025. Eligible studies included adult patients undergoing surgical excision of histologically confirmed BCC or cSCC, with preoperative margin evaluation using either dermoscopy or clinical examination. The primary outcome was the rate of complete histological excision. Study quality was assessed using the Newcastle–Ottawa Scale. A random-effects meta-analysis using the Freeman–Tukey transformation was performed. Results: Nine cohort studies comprising 900 NMSC lesions were included. Dermoscopy-guided excision demonstrated pooled histological clearance of 98.7% (95% CI: 97–99.8%), compared to 80–94% with clinical assessment. Moderate heterogeneity was observed (I2 = 42%). However, variability in study design and limited data for cSCC restricted broader conclusions. Conclusions: Dermoscopy may enhance margin assessment and histological clearance in NMSC surgery, especially for BCC. Further standardized, high-quality studies are needed to confirm its role in surgical planning and extend evidence to SCC.

Background: Temporomandibular disorders (TMDs) encompass a group of conditions characterized by anatomical, histological, and/or functional abnormalities that affect the muscular and/or articular components of the temporomandibular joint. Prolotherapy is an injectable treatment modality for chronic musculoskeletal pain that involves dextrose solution administration in the joint. Aims: To summarize, the aims involve considering the existing quality of clinical evidence on the efficacy of prolotherapy versus placebo and other active comparators, such as autologous blood products or botulinum toxin, in improving the outcomes of TMDs. Methods: A literature search in MEDLINE, Scopus, and Cochrane databases was performed, following the PRISMA statement guidelines, to identify randomized controlled trials (RCTs) of patients with TMDs receiving prolotherapy. The maximal incisor opening (MIO), visual analogue score (VAS) for pain, and frequency of dislocations were analyzed as the outcomes. The weighted mean difference was used to pool outcomes. The risk of bias was recorded for the included studies. Results: Six studies comparing prolotherapy to placebo were identified. Prolotherapy is uniformly more efficient in reducing the VAS for pain when compared to the placebo (mean difference = 1.20, 95%CI: 0.56–1.84, p < 0.001). Perceived jaw mobility was improved among prolotherapy patients, (mean difference = 0.47, 95%CI: 0.05–0.90, p = 0.003) when compared to the placebo. A beneficial effect for prolotherapy with regard to MIO (mean difference = 0.84, 95%CI: −2.12–3.80, p = 0.58) was not confirmed. Prolotherapy appears to be more efficient than autologous blood products in reducing VAS for pain (mean difference = 0.49, 95%CI: 0.11–0.87, p = 0.01). Prolotherapy was found to be more effective in reducing pain, MIO, and clicking when compared to an occlusal splint in a single study. Conclusions: Prolotherapy is also a promising modality for TMDs, despite the limited number of randomized clinical trials. Existing evidence supports its use to reduce TMD-related pain, even against other modalities. Further research is needed to better describe the benefit of prolotherapy for other outcomes.

Objectives: This systematic review and meta-analysis evaluated the clinical utility of superficial temporal vessels as recipient vessels for free flap reconstruction in the maxillofacial region. Given their favourable anatomy and potential advantages in previously treated or vessel-depleted necks, we synthesised available evidence on complication rates, flap viability, and recipient site morbidity. Material and Methods: Following PRISMA guidelines, a comprehensive literature search was performed. Studies were included if they reported outcomes of free flap maxillofacial reconstructions using temporal vessels for microvascular anastomosis. Primary outcomes were arterial and venous thrombosis or compromise, and overall vascular complications. Secondary outcomes included return to theatre, flap necrosis, salvage rates, and recipient site complications. A random-effects model was used for data pooling, and heterogeneity was assessed via the I2 statistic. Results: Twenty-one studies reporting 773 reconstructions in 759 patients were included. Arterial thrombosis/compromise occurred in 1.44%, venous in 5.13%, with an overall vascular complication rate of 7.24%. Return to theatre occurred in 7.72% and flap salvage in 4.23%. Partial and total flap necrosis rates were 2.14% and 4.05% respectively. Recipient site complications were reported in 10.43% of cases. Conclusions: Superficial temporal vessels demonstrate reliable outcomes with complication rates comparable to cervical vessels. Their use may reduce surgical morbidity and should be considered a viable primary recipient option in complex head and neck reconstructions.

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication in patients treated with antiresorptive or antiangiogenic agents, particularly those with cancer-related comorbidities. This systematic review and meta-analysis aimed to estimate the prevalence of free flap failure in patients undergoing microvascular reconstruction for MRONJ. Methods: A comprehensive literature search was conducted across Medline/PubMed, Scopus, and Web of Science up to 30 January 2025. Inclusion criteria were observational studies involving MRONJ patients treated with free flap reconstruction. Risk of bias was assessed using the Newcastle–Ottawa Scale. The pooled prevalence of free flap failure was calculated using a random-effects model with Freeman–Tukey double arcsine transformation. Results: Twelve studies were included in the quantitative analysis. The fibula free flap was the most frequently used flap. The pooled prevalence of free flap failure was 0.1% (95% CI: 0–2.3%), with no significant associations observed in meta-regression analyses for publication year, patient age, or sex. All included studies were of moderate methodological quality. Conclusions: These findings suggest that free flap reconstruction is a reliable and effective surgical option for managing advanced MRONJ in well-resourced and specialized healthcare settings; however, limitations such as small sample sizes and heterogeneity in protocols must be considered. Further high-quality, multicenter studies are needed to evaluate long-term outcomes and refine perioperative management strategies.

PurposeThe aim of this study is to compare the outcomes of vascular anastomosis using loupes magnification versus operative microscope magnification in reconstructive surgery.MethodsWe performed a systematic review of MEDLINE (via PubMed), Scopus and Cochrane Library database according to the PRISMA guidelines. Comparative studies between the two techniques and single arm studies reporting on loupes reconstruction were included. Random-effects model meta-analyses were performed.ResultsTwelve studies, reporting a total of 3908 of flaps, 3409 of which were performed under loupes magnification and 499 under the operative microscope magnification were selected for analysis. No statistically significant differences were observed regarding total flap loss and vascular complication between the two arms. In the Loupes group the rate of total flap loss was 2.65% (95% CI: 1.15–4.63) and the rate of vascular complications 4.49% (95% CI: 2.58–6.84).ConclusionLoupes magnification under circumstances can provide a safe and effective alternative to microvascular reconstruction in reconstructive surgery. With respect to flap failure and vascular complication rates, there appear to be no statistically significant differences between the anastomoses conducted under Loupes magnification and the standard operative microscope.