The risk of PD-L1 expression misclassification in triple-negative breast cancer.

PURPOSE: Stratification of patients with triple-negative breast cancer (TNBC) for anti-PD-L1 therapy is based on PD-L1 expression in tumor biopsies. This study sought to evaluate the risk of PD-L1 misclassification. METHODS: We conducted a high-resolution analysis on ten surgical specimens of TNBC. First, we determined PD-L1 expression pattern distribution via manual segmentation and measurement of 6666 microscopic clusters of positive PD-L1 immunohistochemical staining. Then, based on these results, we generated a computer model to calculate the effect of the positive PD-L1 fraction, aggregate size, and distribution of PD-L1 positive cells on the diagnostic accuracy. RESULTS: Our computer-based model showed that larger aggregates of PD-L1 positive cells and smaller biopsy size were associated with higher fraction of false results (P < 0.001, P < 0.001, respectively). Additionally, our model showed a significant increase in error rate when the fraction of PD-L1 expression was close to the cut-off (error rate of 12.1%, 0.84%, and 0.65% for PD-L1 positivity of 0.5-1.5%, ≤ 0.5% ,and ≥ 1.5%, respectively, P < 0.0001). Interestingly, false positive results were significantly higher than false negative results (0.51-22.62%, with an average of 6.31% versus 0.11-11.36% with an average of 1.58% for false positive and false negative results, respectively, P < 0.05). Furthermore, heterogeneous tumors with different aggregate sizes in the same tumor, were associated with increased rate of false results in comparison to homogenous tumors (P < 0.001). CONCLUSION: Our model can be used to estimate the risk of PD-L1 misclassification in biopsies, with potential implications for treatment decisions.

ACKR2 limits skin fibrosis and hair loss through IFN-ß.

The resolution of inflammation facilitates proper wound healing and limits tissue repair short of exaggerated fibrotic scarring. The atypical chemokine receptor (ACKR)2/D6 scavenges inflammatory chemokines, while IFN-ß is a recently unveiled pro-resolving cytokine. Both effector molecules limit acute inflammatory episodes and promote their resolution in various organs. Here, we found fibrotic skin lesions from ACKR2-/- mice presented increased epidermal and dermal thickening, atrophy of the subcutaneous adipose tissue, augmented disorientation of collagen deposition, and enhanced deformation and loss of hair follicles compared to WT counterparts. In addition, affected skin sections from ACKR2-/- mice contained reduced levels of the pro-resolving mediators IFN-ß and IL-10, but increased levels of the pro-inflammatory chemokines CCL2 and 3, the pro-fibrotic cytokine TGF-ß, and the immune-stimulating cytokine IL-12. Notably, treatment with exogenous IFN-ß rescued, at least in part, all the pro-fibrotic outcomes and lesion size in ACKR2-/- mice and promoted expression of the pro-resolving enzyme 12/15-lipoxygenase (LO) in both ACKR2-/- and WT mice. Moreover, Ifnb-/- mice displayed enhanced pro-fibrotic indices upon exposure to bleomycin. These findings suggest ACKR2 is an important mediator in limiting inflammatory skin fibrosis and acts via IFN-ß production to promote the resolution of inflammation and minimize tissue scaring.

Effects of COVID-19 Lockdowns on the Development of Educational, Social and Emotional Gaps among Children: A Retrospective Chart Review.

BACKGROUND: School closures due to the coronavirus disease 2019 (COVID-19) outbreak affected students physically, socially, and psychologically with an increase in the number of children and adolescent presenting with anxiety, depression, and drug abuse. OBJECTIVES: To examine the impact of COVID-19 and lockdown on the mental health of minors during the pandemic period and to characterize the type and number of referrals to a regional psychiatric outpatient clinic. METHODS: This study included 380 children evaluated in an outpatient child psychiatric clinic. They were divided into two groups: before the lockdowns (BLD) (n=248), from January 2019 to February 2020, and during the lockdowns (LD) (n=132), from March 2020 to April 2021. RESULTS: When comparing the LD to BLD, there was increase in suicide attempts (9.8% vs. 2.8%) and in the use of psychotherapy (81% vs. 56%). There was a decrease in the diagnoses of behavior disorders (29.5% vs. 44.8%) and ADHD (29.5% vs. 50%); as well as a decrease in stimulant usage (22.7% vs. 38%). There was a statistically non-significant increase in the number of children with depression, anxiety, and drug-use disorder. CONCLUSIONS: Many children developed educational, social, emotional, and behavioral gaps during LD, and they lost skills to deal with everyday problems due to social isolation. It is important to follow the long-term impact of the lockdowns and social isolation.

Computerized image analysis of blood vessels within mucosal defects for the prediction of delayed bleeding following colonic endoscopic mucosal resection: a pilot study.

BACKGROUND : Clinically significant post-endoscopic bleeding (CSPEB) is a common complication following colonic endoscopic mucosal resection (EMR). Current prediction tools are clinical and do not use the appearance of the post-EMR mucosal defect. We aimed to predict CSPEB by analyzing blood vessel morphology within the post-EMR mucosal defect. METHODS : 43 patients with CSPEB were matched to 43 non-bleeders for clinical variables associated with CSPEB. Computerized image analysis quantified the morphologic characteristics of the blood vessels in the defect. Variables were measured in relation to the mucosal defect area. Multivariate analysis and a neural network (NNET) were used as prediction models. RESULTS : The CSPEB group vessels had larger maximum diameter (113.07 vs. 69.03; P < 0.001), larger minimum radius (5.09 vs. 3.28; P = 0.002), larger perimeter value (337.82 vs. 193.86; P < 0.001), larger vessel length-of-outline (351.83 vs. 220.68; P = 0.002), and larger fractal dimension (1.11 vs. 1.10; P = 0.005) compared with non-bleeders. Discriminant analysis yielded 86 % sensitivity and 76.7 % specificity and an NNET classifier yielded 100 % sensitivity and 76.9 % specificity for identifying patients at risk. CONCLUSIONS : Blood vessel morphology in the post-EMR defect can be used to predict bleeding following colonic EMR.

The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer.

OBJECTIVES: We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). MATERIALS METHODS: Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. RESULTS: The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. CONCLUSIONS: Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

Histomorphometric Findings May Help Predicting Response in Patients with Chronic Liver Disease.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin. OBJECTIVES: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin. METHODS: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information. RESULTS: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity. CONCLUSIONS: Histomorphometry may help to predict a patient's response to treatment at an early stage.

Cell-centred meta-analysis reveals baseline predictors of anti-TNFα non-response in biopsy and blood of patients with IBD.

OBJECTIVE: Although anti-tumour necrosis factor alpha (anti-TNFα) therapies represent a major breakthrough in IBD therapy, their cost-benefit ratio is hampered by an overall 30% non-response rate, adverse side effects and high costs. Thus, finding predictive biomarkers of non-response prior to commencing anti-TNFα therapy is of high value. DESIGN: We analysed publicly available whole-genome expression profiles of colon biopsies obtained from multiple cohorts of patients with IBD using a combined computational deconvolution-meta-analysis paradigm which allows to estimate immune cell contribution to the measured expression and capture differential regulatory programmes otherwise masked due to variation in cellular composition. Insights from this in silico approach were experimentally validated in biopsies and blood samples of three independent test cohorts. RESULTS: We found the proportion of plasma cells as a robust pretreatment biomarker of non-response to therapy, which we validated in two independent cohorts of immune-stained colon biopsies, where a plasma cellular score from inflamed biopsies was predictive of non-response with an area under the curve (AUC) of 82%. Meta-analysis of the cell proportion-adjusted gene expression data suggested that an increase in inflammatory macrophages in anti-TNFα non-responding individuals is associated with the upregulation of the triggering receptor expressed on myeloid cells 1 (TREM-1) and chemokine receptor type 2 (CCR2)-chemokine ligand 7 (CCL7) -axes. Blood gene expression analysis of an independent cohort, identified TREM-1 downregulation in non-responders at baseline, which was predictive of response with an AUC of 94%. CONCLUSIONS: Our study proposes two clinically feasible assays, one in biopsy and one in blood, for predicting non-response to anti-TNFα therapy prior to initiation of treatment. Moreover, it suggests that mechanism-driven novel drugs for non-responders should be developed.

Effects of Timing of Extracorporeal Shock Wave Therapy on Mandibular Distraction Osteogenesis: An Experimental Study in a Rat Model.

PURPOSE: Distraction osteogenesis (DO) is an established method for bone lengthening in the craniofacial skeleton. Its major drawback is the long consolidation period with attendant morbidity and possible complications. Several methods have been suggested to shorten the consolidation period. We evaluated the timing and effects of extracorporeal shock wave therapy (ESWT) on bone mineralization and extracellular bone matrix proteins during mandibular DO. MATERIALS AND METHODS: Twenty-seven rats underwent mandibular DO (latency period, 3 days; distraction period, 10 days; 0.5 mm/day) and were divided into 3 groups according to the timing of ESWT application: group I (control) received no treatment, whereas groups II and III received ESWT (0.18 mJ/mm2) before and after the active distraction period, respectively. The distracted mandibles were harvested after 4 weeks of consolidation and analyzed radiographically, histologically, and immunohistochemically. RESULTS: Group III showed significantly increased mineral density, enhanced bone formation, a higher collagen orientation index, and greater expression of type I collagen and osteocalcin proteins. CONCLUSIONS: Application of ESWT after active distraction enhances bone maturation and mineralization.

Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction.

OBJECTIVE: Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. DESIGN: We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1ß correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice. RESULTS: A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology. Increased colonic tumor necrosis factor (TNF)α, IL-1ß and IL-6 expression was observed at two different time points. Adherent microbiota from RP differed from those in uninvolved segments and was associated with tissue damage. Using bacterial-epithelial co-cultures, postradiation microbiota enhanced IL-1ß and TNFα expression compared with naïve microbiota. GF mice colonisation by irradiated microbiota versus controls predisposed mice to both radiation injury and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated intestinal radiation injury. CONCLUSIONS: The results demonstrate that rectal radiation induces dysbiosis, which transmits radiation and inflammatory susceptibility and provide evidence that microbial-induced radiation tissue damage is at least in part mediated by IL-1ß. Environmental factors may affect the host via modifications of the microbiome and potentially allow for novel interventional approaches via its manipulation.

Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring.

BACKGROUND: Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use. However, currently, ctDNA is not used for monitoring treatment response. The high prevalence of KRAS hotspot mutations in PDAC suggests that mutant KRAS can be an efficient ctDNA marker for PDAC monitoring. SUBJECTS, MATERIALS, AND METHODS: Seventeen metastatic PDAC patients were recruited and serial plasma samples were collected. CtDNA was extracted from the plasma, and KRAS mutation analysis was performed using next-generation sequencing and correlated with serum CA19-9 levels, imaging, and survival. RESULTS: Plasma KRAS mutations were detected in 5/17 (29.4%) patients. KRAS ctDNA detection was associated with shorter survival (8 vs. 37.5 months). Our results show that, in ctDNA positive patients, ctDNA is at least comparable to CA19-9 as a marker for monitoring treatment response. Furthermore, the rate of ctDNA change was inversely correlated with survival. CONCLUSION: Our results confirm that mutant KRAS ctDNA detection in metastatic PDAC patients is a poor prognostic marker. Additionally, we were able to show that mutant KRAS ctDNA analysis can be used to monitor treatment response in PDAC patients and that ctDNA dynamics is associated with survival. We suggest that ctDNA analysis in metastatic PDAC patients is a readily available tool for disease monitoring. IMPLICATIONS FOR PRACTICE: Avoiding futile chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring response to treatment is of utmost importance. A novel biomarker for monitoring treatment response in PDAC, using mutant KRAS circulating tumor DNA (ctDNA), is proposed. Results, although limited by small sample numbers, suggest that ctDNA can be an effective marker for disease monitoring and that ctDNA level over time is a better predictor of survival than the dynamics of the commonly used biomarker CA19-9. Therefore, ctDNA analysis can be a useful tool for monitoring PDAC treatment response. These results should be further validated in larger sample numbers.

Severe cytomegalovirus enterocolitis developing following daratumumab exposure in three patients with multiple myeloma.

OBJECTIVES: The risk of cytomegalovirus (CMV) reactivation in multiple myeloma (MM) patients treated with bortezomib-based induction regimens is increased following autologous stem cell transplantation (ASCT). There is paucity of data regarding the risk of CMV infections in MM patients who did not receive bortezomib and ASCT. METHODS: We herein report three cases of heavily pretreated MM patients, receiving daratumumab-containing combination regimens, in whom ASCT had been performed long ago and who recently developed severe CMV-related gastrointestinal disease. RESULTS: All the three patients had a prolonged CMV disease course requiring a long-term antiviral treatment. All the patients suffered from CMV colitis. One patient had concurrent CMV duodenitis and another patient had a concurrent CMV retinitis. CONCLUSION: Novel myeloma treatments prolong patient survival and more patients with profound immunosuppression following multiple lines of therapies are seen in clinical practice. These patients may present with opportunistic infections that were rare in the past. Our findings suggest a possible association between daratumumab therapy (in combination with other immunosuppressive therapies) and severe CMV gastrointestinal disease. A longer follow-up is needed to explore long-term side effects of novel agents like daratumumab in newly diagnosed as well as heavily pretreated MM patients.

Evaluation of Microscopic Changes in Fallopian Tubes of BRCA Mutation Carriers by Morphometric Analysis of Histologic Slides: A Preliminary Pilot Study.

Mutations in BRCA genes increase the risk of ovarian cancer, yet no method for early diagnosis is available. Some serous ovarian tumors are hypothesized to stem from cells of the fallopian tube fimbria. Using a novel method of computerized morphometry of the fimbrial epithelium, this study aimed to detect morphologic differences in noncancerous fimbriae between BRCA mutation carriers and noncarriers, and between healthy and serous ovarian cancer patients. Twenty-four fimbriae from healthy women (13 BRCA+, 11 BRCA-) and 21 fimbriae from women with serous ovarian cancer (10 BRCA+, 11 BRCA-), all reported as "normal" by hematoxylin and eosin examination, were subjected to computerized histomorphometric analysis. A Fast Fourier Transformation was applied to images of fimbrial epithelium and the Fast Fourier Transformation 2-dimensional frequency maps were subsequently quantified for nuclear orientation and planar distribution by a cooccurrence matrix analysis. Additional analysis of nuclear contour was applied to the fimbriae of the healthy women. Among the healthy women, significant differences were found in morphometric characteristics between the BRCA mutation carriers and noncarriers. Among the women with ovarian cancer, no significant differences were found between BRCA mutation carriers and noncarriers. Between healthy women and those with ovarian cancer, significant differences were detected, regardless of BRCA mutational status. A novel method, which combined Fast Fourier Transformation with cooccurrence matrix analysis, demonstrated differences in morphometric characteristics in the fimbriae between healthy and ovarian cancer patients, and between BRCA mutation carriers and noncarriers. The clinical significance of these observations should be investigated.

Method Used for Tumor Bed Closure (Suture vs. Sealant), Ischemia Time and Duration of Surgery are Independent Predictors of Post-Nephron Sparing Surgery Acute Kidney Injury.

INTRODUCTION: The aim of our study was to examine the influence of tumor complexity and operative variables on the degree and rate of post-nephron sparing surgery (NSS) acute kidney injury (AKI). METHODS: We retrospectively reviewed the records of 477 patients who underwent NSS for enhancing renal masses in our institution. AKI was determined using the latest definition by AKIN and RIFLE criteria. Serum creatinine was assessed daily starting from day 1 post-surgery and until discharge (usually on postoperative day 3). Estimated glomerular filtration was determined using the Modification of Diet in Renal Disease equation. RESULTS: Overall, 191 patients (40%) developed postoperative AKI, and most of them (88%) were grade 1. Multivariate analysis revealed that the most significant and independent variables associated with AKI were operation time (p = 0.02), ischemia time (p = 0.02), and the use of tissue adhesive for tumor bed closure (p = 0.02). Other important factors (by univariate analysis) were the need for blood transfusion (p = 0.003) and estimated blood loss (p = 0.007). CONCLUSIONS: Operative time, ischemia, and tumor bed closure method are independent predictors of post-NSS AKI. Efforts should be made to limit prolonged ischemia and to reduce viable parenchymal loss. Further studies concerning the functional impact of AKI in these patients will be required.

Cancer-associated fibroblasts are an infrequent finding in the microenvironment of proliferative verrucous leukoplakia-associated squamous cell carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are generally associated with negative prognostic factors. This study compares the clinicopathologic impact of CAFs in oral squamous cell carcinoma in patients with a history of proliferative verrucous leukoplakia (p-scca) and patients with conventional squamous cell carcinoma of the buccal mucosa, gingiva, and palate (c-scca). METHODS: A retrospective clinicopathologic and immunohistochemical analysis of 97 tumor specimens from 78 patients (13 patients with proliferative verrucous leukoplakia-associated squamous cell carcinoma (n = 32) and conventional squamous cell carcinoma from the buccal mucosa, gingiva, and palate (n = 65) was conducted. Immunostaining with anti-alpha-smooth muscle actin (α-SMA) antibody was used to evaluate the presence of CAFs. RESULTS: α-SMA expression was an infrequent finding in p-scca and seen in only 6% of p-scca compared to 40% of c-scca (P < 0.0004). In the c-scca subgroup, α-SMA significantly correlated with tumor size (T) (P = 0.009), tumor thickness (P < 0.0009), perineural invasion (P = 0.009), and microscopic grade (P = 0.018). CONCLUSIONS: The presence of CAFs was an infrequent finding in our p-scca cohort which may contribute to its seemingly slower growing and less invasive growth pattern. In the cohort of c-scca patients, higher levels of CAFs correlated with microscopic invasiveness, tumor size, and perineural invasion. Practically, these are important observations as targeting strategies are being developed to combat carcinoma types where CAFs significance has been validated.

IUGR induced by maternal chronic inflammation: long-term effect on offspring's ovaries in rat model-a preliminary report.

PURPOSE: Excess maternal inflammation and oxidative stress while in utero have been known to affect gross fetal development. However, an association between the inflammatory process in utero and the effects on ovarian development and future fertility has not yet been demonstrated. This study focused on LPS-induced chronic inflammation in early pregnancy and its effect on ovarian development and reserves of the offspring, using a rat model. Our aim was to determine whether maternal inflammation in utero disturbs reproductive system development in the offspring, given that maternal inflammation and oxidative stress has been shown to affect gross fetal development. METHODS: Prospective case control rat model. Sprague-Dawley pregnant rats (n = 11) received intraperitoneal lipopolysaccharide (LPS group) (50 µg/kg bodyweight) or saline solution (control group) on day 14, 16, and 18 of gestation. Pups were delivered spontaneously. At 3 months, female offspring were weighed and killed. Ovaries were harvested for (1) follicle count using hematoxylin and eosin staining, (2) apoptosis: ovaries were stained for caspase, and (3) serum CRP and AMH levels were determined. RESULTS: Birth weights of pups were significantly lower in the LPS group compared to the control group (6.0 ± 0.6 vs. 6.6 ± 0.4 gr; P = 0.0003). The LPS group had fewer preantral follicles, and increased intensity of Caspase 3 staining (510 vs. 155.5 u; P = 0.007). AMH levels were significantly lower in the LPS group (4.15 ± 0.46 vs 6.08 ± 1.88 ng/ml; P = 0.016). There was no significant difference in the CRP and MCP-1 levels between the two groups. CONCLUSIONS: Chronic maternal inflammation induced intrauterine growth restriction in offspring and a decrease in the proportion of follicles. This change might be due to premature apoptosis. These preliminary results suggest that maternal inflammation has a detrimental effect on the development of the female reproductive system of the offspring and thus, future fertility.

p27 and its ubiquitin ligase Skp2 expression in endometrium of IVF patients with repeated hormonal stimulation.

This preliminary study examined a possible effect of long duration repeated hormonal stimulation on the endometrium using a molecular tool. The expression of the hormone stimulated, cell cycle regulators, p27 and its ligase S-phase kinase-interacting protein2 (Skp2), were assessed in 46 endometrial samples of patients who underwent repeated IVF cycles (3-21). Skp2 protein is usually undetectable in normal tissue and can be demonstrated only in rapidly dividing cells. Samples from non-stimulated, normal cycling women served as control group A. Samples of endometrial carcinoma served as control group B. In secretory endometrium, the expression of p27 was found to be lower and Skp2 higher in the study group compared with control group A. Moreover, in 25% of patients of the study group, Skp2 expression was significantly higher (P < 0.05) compared with control group A, reaching concentrations demonstrated in endometrial carcinoma. The findings of this study suggest that repeated hormone stimulation cycles may disrupt endometrial physiology, potentially towards abnormal proliferation. These changes in protein expression are described for the first time in IVF patients and should be further investigated.

In vivo assessment of aged human skin with a unilateral NMR scanner.

Human skin undergoes morphological and biochemical changes as a result of chronological aging and exposure to solar ultraviolet irradiation (photoaging). Noninvasive detection of these changes may aid in the prevention and treatment of both types of aging. This article presents a noninvasive method for the evaluation of aging skin with a unilateral stray field NMR scanner. These portable and inexpensive scanners may be suitable for in-depth skin characterization. In vivo profiles of sun-protected and sun-exposed skin from the forearms of female subjects of different ages (n = 9) were measured. Skin biopsies for histopathological examination were used as reference. T2 analysis with a bi-exponential decay model was applied and the extracted parameters were examined as markers for dermal aging. In the upper reticular dermis, a significant increase in the fraction of the slow T2 component and in the T2 value itself was found to correlate with chronological aging. For most subjects, there was an additional increase in the values of the slow T2 component and the T2 values from the sun-exposed forearm, superimposed on that measured for the sun-protected forearm. These results are in agreement with the decline in collagen content and the increase in free water content with aging. The results suggest that such a technique can be used as a tool for the assessment of aging, and that bi-exponential fitting can produce sensitive fingerprint parameters for the dermal alterations that occur during aging.

A deep penetrating facial congenital melanocytic tumor with bone involvement and ipsilateral eye blindness.

Bone involvement has been described in tumors with melanocytic differentiation such as melanotic neuroectodermal tumor of infancy, and very rarely in cellular blue nevi and neurocristic cutaneous hamartoma. We present an unusual case of facial congenital melanocytic tumor that involved the underlying bones and maxillary sinus and led to unilateral blindness. A newborn with a large red bluish patch with peripheral brown and black macules overlying marked swelling on the left side of his face was presented. The tumor was shown by magnetic resonance imaging, scintigraphy, and histopathology to invade the underlying bones and maxillary sinus and to compress the left eyeball resulting in blindness. Histopathology, immunohistochemistry, morphometric computerized microscopy, molecular genetic mutation analysis, and fluorescent in situ hybridization studies were more congruent with a melanocytic nevus. An 8.5-year follow-up was uneventful, with spontaneous partial shrinkage of the tumor.