Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.

BACKGROUND: Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). AIMS: This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC. METHODS: Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis. RESULTS: Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks. CONCLUSIONS: Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.

Association between Sarcopenia and Survival in Patients Undergoing Gamma Knife Surgery for Brain Metastasis from Breast Cancer: A Retrospective Single-centre Cohort Study.

AIMS: Many recent studies related to cancer surgery have reported that sarcopenia influences mortality in surgical patients. However, few comprehensive studies have examined the associations between sarcopenia and short- and long-term surgical outcomes of metastatic cancer, especially breast cancer with brain metastasis. In the present study, we investigated the association between sarcopenia and mortality in patients who underwent gamma knife radiosurgery (GKRS) for brain metastasis with breast cancer. MATERIALS AND METHODS: This retrospective study analysed 157 patients who underwent GKRS for brain metastasis with breast cancer between January 2014 and December 2018. A Cox regression analysis was carried out to evaluate the association between sarcopenia and mortality at 90 days, 180 days, 1 year, 3 years and the overall period. RESULTS: In the Cox regression analysis, sarcopenia was significantly associated with high 90-day mortality (adjusted hazard ratio 3.46, 95% confidence interval 1.24-9.67, P = 0.018), 180-day mortality (adjusted hazard ratio 2.67, 95% confidence interval 1.37-5.22, P = 0.004), 1-year mortality (adjusted hazard ratio 2.39, 95% confidence interval 1.42-4.02, P = 0.001), 3-year mortality (adjusted hazard ratio 2.39, 95% confidence interval 1.53-3.74, P < 0.001) and overall mortality (adjusted hazard ratio 2.11, 95% confidence interval 1.37-3.26, P < 0.001). CONCLUSION: Sarcopenia could be a risk factor for short- and long-term mortality in patients undergoing GKRS for brain metastasis from breast cancer.

Mortality Risk Factors in Pediatric Onco-Critical Care Patients and Machine Learning Derived Early Onco-Critical Care Phenotypes in a Retrospective Cohort.

OBJECTIVES: To use supervised and unsupervised statistical methodology to determine risk factors associated with mortality in critically ill pediatric oncology patients to identify patient phenotypes of interest for future prospective study. DESIGN: This retrospective cohort study included nonsurgical pediatric critical care admissions from January 2017 to December 2018. We determined the prevalence of multiple organ failure (MOF), ICU mortality, and associated factors. Consensus k-means clustering analysis was performed using 35 bedside admission variables for early, onco-critical care phenotype development. SETTING: Single critical care unit in a subspeciality pediatric hospital. INTERVENTION: None. PATIENTS: There were 364 critical care admissions in 324 patients with underlying malignancy, hematopoietic cell transplant, or immunodeficiency reviewed. MEASUREMENTS: Prevalence of multiple organ failure, ICU mortality, determination of early onco-critical care phenotypes. MAIN RESULTS: ICU mortality was 5.2% and was increased in those with MOF (18.4% MOF, 1.7% single organ failure [SOF], 0.6% no organ failure; p ≤ 0.0001). Prevalence of MOF was 23.9%. Significantly increased ICU mortality risk was associated with day 1 MOF (hazards ratio [HR] 2.27; 95% CI, 1.10-6.82; p = 0.03), MOF during ICU admission (HR 4.16; 95% CI, 1.09-15.86; p = 0.037), and with invasive mechanical ventilation requirement (IMV; HR 5.12; 95% CI, 1.31-19.94; p = 0.018). Four phenotypes were derived (PedOnc1-4). PedOnc1 and 2 represented patient groups with low mortality and SOF. PedOnc3 was enriched in patients with sepsis and MOF with mortality associated with liver and renal dysfunction. PedOnc4 had the highest frequency of ICU mortality and MOF characterized by acute respiratory failure requiring invasive mechanical ventilation at admission with neurologic dysfunction and/or severe sepsis. Notably, most of the mortality in PedOnc4 was early (i.e., within 72 hr of ICU admission). CONCLUSIONS: Mortality was lower than previously reported in critically ill pediatric oncology patients and was associated with MOF and IMV. These findings were further validated and expanded by the four derived nonsynonymous computable phenotypes. Of particular interest for future prospective validation and correlative biological study was the PedOnc4 phenotype, which was composed of patients with hypoxic respiratory failure requiring IMV with sepsis and/or neurologic dysfunction at ICU admission.

Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis.

BACKGROUND: One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network's objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis. METHODS: We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis without hyperferritinemia. Causal inference analysis of these 41 variables, MAS, and mortality was performed. RESULTS: Mortality was increased in children with hyperferritinemic sepsis (27/117, 23% vs 16/280, 5.7%; Odds Ratio = 4.85, 95% CI [2.55-9.60]; z = 4.728; P-value < 0.0001). Hyperferritinemic sepsis had higher C-reactive protein, sCD163, IL-22, IL-18, IL-18 binding protein, MIG/CXCL9, IL-1ß, IL-6, IL-8, IL-10, IL-17a, IFN-γ, IP10/CXCL10, MCP-1/CCL2, MIP-1α, MIP-1ß, TNF, MCP-3, IL-2RA (sCD25), IL-16, M-CSF, and SCF levels; lower ADAMTS13 activity, sFasL, whole blood ex vivo TNF response to endotoxin, and TRAIL levels; more Adenovirus, BK virus, and multiple virus DNAemias; and more MAS (P-value < 0.05). Among these variables, only MCP-1/CCL2 (the monocyte chemoattractant protein), MAS, and ferritin levels were directly causally associated with mortality. MCP-1/CCL2 and hyperferritinemia showed direct causal association with depressed ex vivo whole blood TNF response to endotoxin. MCP-1/CCL2 was a mediator of MAS. MCP-1/CCL2 and MAS were mediators of hyperferritinemia. CONCLUSIONS: These findings establish hyperferritinemic sepsis as a high-risk condition characterized by increased cytokinemia, viral DNAemia, thrombotic microangiopathy, immune depression, macrophage activation syndrome, and death. The causal analysis provides rationale for designing anti-inflammatory trials that reduce macrophage activation to improve survival and enhance infection clearance in pediatric hyperferritinemic sepsis.

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Videolaryngoscopy vs. flexible fibrescopy for tracheal intubation in patients with cervical spine immobilisation: a randomised controlled trial.

In patients with cervical spine immobilisation, tracheal intubation devices other than a direct laryngoscope are frequently used to facilitate tracheal intubation and avoid related complications. In this randomised controlled trial, we compared videolaryngoscopic and fibrescopic tracheal intubation in patients with a cervical collar. Tracheal intubation was performed using either a videolaryngoscope with a non-channelled Macintosh blade (n = 166) or a flexible fibrescope (n = 164) in patients having elective cervical spine surgery whose neck was immobilised with a cervical collar to simulate a difficult airway. The primary outcome was the first attempt success rate of tracheal intubation. Secondary outcomes were the overall success rate of tracheal intubation; time to tracheal intubation; use of additional airway manoeuvres; and incidence and severity of tracheal intubation-related airway complications. First attempt success rate was higher in the videolaryngoscope group than in the fibrescope group (164/166 (98.8%) vs. 149/164 (90.9%), p = 0.003). Tracheal intubation was successful within three attempts in all patients. Median (IQR [range]) time to tracheal intubation was shorter (50.0 (41.0-72.0 [25.0-170.0]) s vs. 81.0 (65.0-107.0 [24.0-178.0]) s, p < 0.001) and additional airway manoeuvres were less frequent (30/166 (18.1%) vs. 91/164 (55.5%), p < 0.001) in the videolaryngoscope group compared with the fibrescope group. The incidence and severity of intubation-related airway complications were not different between the two groups. When performing tracheal intubation in patients with a cervical collar, videolaryngoscopy with a non-channelled Macintosh blade was superior to flexible fibrescopy.

Deep-learning model associating lateral cervical radiographic features with Cormack-Lehane grade 3 or 4 glottic view.

Unanticipated difficult laryngoscopy is associated with serious airway-related complications. We aimed to develop and test a convolutional neural network-based deep-learning model that uses lateral cervical spine radiographs to predict Cormack-Lehane grade 3 or 4 direct laryngoscopy views of the glottis. We analysed the radiographs of 5939 thyroid surgery patients at our hospital, 253 (4%) of whom had grade 3 or 4 glottic views. We used 10 randomly sampled datasets to train a model. We compared the new model with six similar models (VGG, ResNet, Xception, ResNext, DenseNet and SENet). The Brier score (95%CI) of the new model, 0.023 (0.021-0.025), was lower ('better') than the other models: VGG, 0.034 (0.034-0.035); ResNet, 0.033 (0.033-0.035); Xception, 0.032 (0.031-0.033); ResNext, 0.033 (0.032-0.033); DenseNet, 0.030 (0.029-0.032); SENet, 0.031 (0.029-0.032), all p < 0.001. We calculated mean (95%CI) of the new model for: R2 , 0.428 (0.388-0.468); mean squared error, 0.023 (0.021-0.025); mean absolute error, 0.048 (0.046-0.049); balanced accuracy, 0.713 (0.684-0.742); and area under the receiver operating characteristic curve, 0.965 (0.962-0.969). Radiographic features around the hyoid bone, pharynx and cervical spine were associated with grade 3 and 4 glottic views.

Is there a clinical difference in paediatric congenital cholesteatoma according to age?

OBJECTIVE: This study aimed to analyse surgical outcomes of paediatric patients with congenital cholesteatoma according to age. METHOD: This was a retrospective study reviewing the records of 186 children (136 boys and 50 girls) from August 1993 to January 2016. Patients were divided into three age groups (equal to or less than 3 years, over 3 and less than 7 years, and 7 to 15 years). RESULTS: There were significant differences in chief complaints, location of cholesteatoma in the middle ear, computed tomography findings, operation methods, ossicular erosion and type of cholesteatoma sac among the three groups. In addition, older age, open type cholesteatoma, ossicular erosion and mastoid invasion of cholesteatoma increased the recurrence rate after surgery. However, despite higher pre-operative air-bone gap in older children, hearing can be improved enough after proper surgery with ossicular reconstruction. CONCLUSION: Delayed detection of paediatric cholesteatoma can lead to extensive disease and the need for an aggressive operation, which can result in worse hearing outcomes and an increased recurrence risk.

Phase Ib study of eprenetapopt (APR-246) in combination with pembrolizumab in patients with advanced or metastatic solid tumors.

BACKGROUND: We conducted a phase I, multicenter, open-label, dose-finding, and expansion study to determine the safety and preliminary efficacy of eprenetapopt (APR-246) combined with pembrolizumab in patients with advanced/metastatic solid tumors (ClinicalTrials.gov NCT04383938). PATIENTS AND METHODS: For dose-finding, requirements were non-central nervous system primary solid tumor, intolerant to/progressed after ≥1 line of treatment, and eligible for pembrolizumab; for expansion: (i) gastric/gastroesophageal junction tumor, intolerant to/progressed after first-line treatment, and no prior anti-programmed cell death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy; (ii) bladder/urothelial tumor, intolerant to/progressed after first-line cisplatin-based chemotherapy, and no prior anti-PD-1/PD-L1 therapy; (iii) non-small-cell lung cancer (NSCLC) with previous anti-PD-1/PD-L1 therapy. Patients received eprenetapopt 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle. Primary endpoints were dose-limiting toxicity (DLT), adverse events (AEs), and recommended phase II dose (RP2D) of eprenetapopt. RESULTS: Forty patients were enrolled (median age 66 years; range 27-85) and 37 received eprenetapopt plus pembrolizumab. No DLTs were reported and the RP2D for eprenetapopt in combination was 4.5 g/day IV on days 1-4. The most common eprenetapopt-related AEs were dizziness (35.1%), nausea (32.4%), and vomiting (29.7%). AEs leading to eprenetapopt discontinuation occurred in 2/37 patients (5.4%). In efficacy-assessable patients (n = 29), one achieved complete response (urothelial cancer), two achieved partial responses (NSCLC, urothelial cancer), and six patients had stable disease. CONCLUSIONS: The eprenetapopt plus pembrolizumab combination was well tolerated with an acceptable safety profile and showed clinical activity in patients with solid tumors.

Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA. PATIENTS AND METHODS: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR). RESULTS: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA. CONCLUSIONS: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches.

In vitro mitochondrial apoptosis of melanoma cells via immature Poncirus trifoliata fruit extract.

OBJECTIVE: Poncirus trifoliata (P. trifoliata) fruits exert phytotherapeutic effects, depending on their maturity level. However, the mechanism by which these phytotherapeutic effects are exerted remains undefined - especially in cancers. Therefore, in this study, we investigated the effects of the immature fruit extract of P. trifoliata on a B16 melanoma cell line. MATERIALS AND METHODS: The effect of immature P. trifoliata extract on B16 cells was evaluated by MTT assay, cell proliferation, FACScan analysis of cell cycles, confocal imaging analysis, nuclear (Hoechst) staining, apoptosis assay (Annexin V-fluorescein isothiocyanate/propidium iodide staining), and Western blot assay. The capacity of immature P. trifoliata extract to inhibit the invasion and migration of B16 cells was assessed using the scratch-wound assay and Matrigel migration assay. The effect of immature P. trifoliata extract on mitochondrial function was determined via the mitochondrial membrane potential assay, activity, and fraction and cytosol proteins. RESULTS: Treating B16 cells with a methanol extract of immature P. trifoliata (MEPT) significantly inhibited cell viability, migration, and invasiveness in a dose- (p<0.01) and time (p<0.01)- dependent manner. MEPT arrested the cells in the G1 phase of the cell cycle and led to the activation of the PI3K/AKT/p21 pathway. Furthermore, MEPT dose-dependently induced apoptosis in B16 cells by increasing the expression of the pro-apoptotic proteins Bax and Apaf-1, while decreasing the expression of the anti-apoptotic protein, Bcl-2. MEPT treatment also decreased mitochondrial membrane potential. CONCLUSIONS: Immature P. trifoliata extract inhibited the growth of melanoma cells by inducing cell apoptosis through mitochondrial pathways. Therefore, further research into immature P. trifoliata extract as a potential therapeutic compound for melanoma treatment is warranted.

Patterns of Regional Failure after Pancreaticoduodenectomy in Patients with Distal Extrahepatic Cholangiocarcinoma: Suggestion of the Clinical Target Volume for Elective Nodal Irradiation.

AIMS: To evaluate the pattern of locoregional recurrence (LRR) after pancreaticoduodenectomy in patients with distal extrahepatic cholangiocarcinoma (DEHC) and to identify an optimal target volume for elective nodal irradiation. MATERIALS AND METHODS: We analysed the medical records of DEHC patients who underwent pancreaticoduodenectomy and had LRR between 1991 and 2015. Among these patients, 30 received adjuvant chemotherapy alone, 14 underwent radiotherapy with or without chemotherapy and 28 received no treatment. After reviewing computed tomography or magnetic resonance imaging scans, the sites of LRR were identified and mapped to the corresponding locations on the representative computed tomography images. RESULTS: In total, 136 LRRs were identified in 72 patients from four institutions. Local recurrences were observed at 44 sites (32.4%): tumour bed in 15, choledochojejunostomy in 25 and pancreaticojejunostomy in four. Regional recurrences were observed at 92 sites (67.6%); the most common site was the portal vein area (n = 18), followed by the para-aortic area (n = 17). Based on the mapped plots of regional recurrence, a clinical target volume covering 90% of regional recurrences was generated using the appropriate margin for the vascular structures of the portal vein, celiac axis, superior mesenteric artery, left gastric artery and aorta. CONCLUSIONS: Given the pattern of LRR, we showed that the nodal clinical target volume based on vascular structures could appropriately cover high-risk regions of nodal involvement. These findings may help physicians construct a target volume in postoperative radiotherapy for DEHC patients undergoing pancreaticoduodenectomy.

A randomised controlled trial of 7.5-mm and 7.0-mm tracheal tubes vs. 6.5-mm and 6.0-mm tracheal tubes for men and women during laparoscopic surgery.

Sore throat after tracheal intubation impairs postoperative recovery. We randomly allocated 172 ASA physical status 1-2 participants, scheduled for laparoscopic lower abdominal surgery, to tracheal intubation with larger tubes (n = 88) or smaller tubes (n = 84), with internal diameters 7.5-mm vs. 6.5-mm for men and 7.0-mm vs. 6.0-mm for women. Primary outcome was the rates of no, mild, moderate or severe sore throat 1 h after surgery, which were 60, 10, 17 and 1 with larger tracheal tubes and 79, 5, 0 and 0 with smaller tubes, p < 0.001. The equivalent rates 24 h after surgery were 64, 16, 8 and 0 vs. 74, 6, 3 and 1, p = 0.037. Intra-operative ventilatory variables were unaffected by tube diameter, including peak inspiratory pressure, plateau pressure and end-tidal carbon dioxide partial pressure. In summary, smaller tracheal tubes benefitted patients having laparoscopic operations.

Effects of melatonin receptor expression on prognosis and survival in oral squamous cell carcinoma patients.

Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour-node-metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma [hazard ratio = 1.423, 95% confidence interval (CI) = 1.019-1.988, p = 0.038]. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development.

Clinical characteristics and differences of 802 acral tumours, categorized by anatomical sites.

BACKGROUND: Acral skin tumours are common, but information in the literature regarding their incidence is scarce. AIM: To investigate the clinical characteristics and differences in incidence of benign and malignant acral tumours by anatomical site. METHODS: A retrospective review was conducted of 802 patients with acral skin tumours confirmed by skin biopsy between January 2010 and December 2019. Age, sex, duration, symptoms and sites were obtained from medical records and photographs. RESULTS: The mean age of onset was 43.8 years, the male/female ratio was 1 : 1.41, and the mean duration was 68.8 months. Most tumours were asymptomatic (66.7%). In total, 802 acral tumours were identified: 512 (63.8%) were benign and 290 (36.2%) were malignant. The most common benign tumours were benign melanocytic lesions (n = 239), and the most common malignant tumours were melanoma (n = 234). The most common site was the sole (n = 408). Benign melanocytic lesions, melanoma and epidermal cysts were more frequent on the foot, whereas pyogenic granuloma, glomus tumours, haemangiomas and mucous cysts were more frequent on the hand. Glomus tumours, fibromas, mucous cysts and osteomas were more frequent on the nail portion, and benign melanocytic lesions and epidermal cysts were more frequent on the non-nail portion. CONCLUSION: This study reports the incidence of various benign and malignant acral tumours according to site, and we believe the results will be helpful in making a clinical diagnosis.

Prognostic Utility of Disproportionately Enlarged Subarachnoid Space Hydrocephalus in Idiopathic Normal Pressure Hydrocephalus Treated with Ventriculoperitoneal Shunt Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Disproportionately enlarged subarachnoid space hydrocephalus is a specific radiologic marker for idiopathic normal pressure hydrocephalus. However, controversy exists regarding the prognostic utility of disproportionately enlarged subarachnoid space hydrocephalus. PURPOSE: Our aim was to evaluate the prevalence of disproportionately enlarged subarachnoid space hydrocephalus in idiopathic normal pressure hydrocephalus and its predictive utility regarding prognosis in patients treated with ventriculoperitoneal shunt surgery. DATA SOURCES: We used MEDLINE and EMBASE databases. STUDY SELECTION: We searched for studies that reported the prevalence or the diagnostic performance of disproportionately enlarged subarachnoid space hydrocephalus in predicting treatment response. DATA ANALYSIS: The pooled prevalence of disproportionately enlarged subarachnoid space hydrocephalus was obtained. Pooled sensitivity, specificity, and area under the curve of disproportionately enlarged subarachnoid space hydrocephalus to predict treatment response were obtained. Subgroup and sensitivity analyses were performed to explain heterogeneity among the studies. DATA SYNTHESIS: Ten articles with 812 patients were included. The pooled prevalence of disproportionately enlarged subarachnoid space hydrocephalus in idiopathic normal pressure hydrocephalus was 44% (95% CI, 34%-54%). The pooled prevalence of disproportionately enlarged subarachnoid space hydrocephalus was higher in the studies using the second edition of the Japanese Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus compared with the studies using the international guidelines without statistical significance (52% versus 43%, P = .38). The pooled sensitivity and specificity of disproportionately enlarged subarachnoid space hydrocephalus for prediction of treatment response were 59% (95% CI, 38%-77%) and 66% (95% CI, 57%-74%), respectively, with an area under the curve of 0.67 (95% CI, 0.63-0.71). LIMITATIONS: The lack of an established method for assessing disproportionately enlarged subarachnoid space hydrocephalus using brain MR imaging served as an important cause of the heterogeneity. CONCLUSIONS: Our meta-analysis demonstrated a relatively low prevalence of disproportionately enlarged subarachnoid space hydrocephalus in idiopathic normal pressure hydrocephalus and a poor diagnostic performance for treatment response.

Periodontal Pathogens Promote Foam Cell Formation by Blocking Lipid Efflux.

Foam cells are one of the major cellular components of atherosclerotic plaques, within which the trace of periodontal pathogens has also been identified in recent studies. In line with these findings, the correlation between periodontitis and atherosclerotic cardiovascular incidences has been repetitively supported by evidence from a number of experimental studies. However, the direct role of periodontal pathogens in altered cellular signaling underlying such cardiovascular events has not been clearly defined. To determine the role of periodontal pathogens in the pathogenesis of atherosclerosis, especially in the evolution of macrophages into foam cells, we monitored the pattern of lipid accumulation within macrophages in the presence of periodontal pathogens, followed by characterization of these lipids and investigation of major molecules involved in lipid homeostasis. The cells were stained with the lipophilic fluorescent dye BODIPY 493/503 and Oil Red O to characterize the lipid profile. The amounts of Oil Red O-positive droplets, representing neutral lipids, as well as fluorescent lipid aggregates were prominently increased in periodontal pathogen-infected macrophages. Subsequent analysis allowed us to locate the accumulated lipids in the endoplasmic reticulum. In addition, the levels of cholesteryl ester in periodontal pathogen-infected macrophages were increased, implying disrupted lipid homeostasis. Further investigations to delineate the key messengers and regulatory factors involved in the altered lipid homeostasis have revealed alterations in cholesterol efflux-related enzymes, such as ABCG1 and CYP46A1, as contributors to foam cell formation, and increased Ca2+ signaling and reactive oxygen species (ROS) production as key events underlying disrupted lipid homeostasis. Consistently, a treatment of periodontal pathogen-infected macrophages with ROS inhibitors and nifedipine attenuated the accumulation of lipid droplets, further confirming periodontal pathogen-induced alterations in Ca2+ and ROS signaling and the subsequent dysregulation of lipid homeostasis as key regulatory events underlying the evolution of macrophages into foam cells.