Rates of Second Tumor, Metastasis, and Death From Cutaneous Squamous Cell Carcinoma in Patients With and Without Transplant-Associated Immunosuppression.

Importance: Cutaneous squamous cell carcinoma (cSCC) may occur with multiple primary tumors, metastasize, and cause death both in immunocompetent and immunosuppressed patients. Objective: To study the rates of second cSCC, metastasis, and death from cSCC in patients with and without organ transplant-associated immunosuppressive treatment. Design, Setting, and Participants: This population-based, nationwide cohort study used Cancer Registry of Norway data from 47 992 individuals diagnosed with cSCC at 18 years or older between January 1, 1968, and December 31, 2020. Data were analyzed between November 24, 2021, and November 15, 2022. Exposures: Receipt of a solid organ transplant at Oslo University Hospital between 1968 and 2012 followed by long-term immunosuppressive treatment. Main Outcomes and Measures: Absolute rates of second cSCC, metastasis, and death from cSCC were calculated per 1000 person-years with 95% CIs. Hazard ratios (HRs) estimated using Cox proportional hazard regression were adjusted for age, sex, and year of first cSCC diagnosis. Results: The study cohort comprised 1208 organ transplant recipients (OTRs) (median age, 66 years [range, 27-89 years]; 882 men [73.0%] and 326 women [27.0%]) and 46 784 non-OTRs (median age, 79 years [range, 18-106 years]; 25 406 men [54.3%] and 21 378 women [45.7%]). The rate of a second cSCC per 1000 person-years was 30.9 (95% CI, 30.2-31.6) in non-OTRs and 250.6 (95% CI, 232.2-270.1) in OTRs, with OTRs having a 4.3-fold increased rate in the adjusted analysis. The metastasis rate per 1000 person-years was 2.8 (95% CI, 2.6-3.0) in non-OTRs and 4.8 (95% CI, 3.4-6.7) in OTRs, with OTRs having a 1.5-fold increased rate in the adjusted analysis. A total of 30 451 deaths were observed, of which 29 895 (98.2%) were from causes other than cSCC. Death from cSCC was observed in 516 non-OTRs (1.1%) and 40 OTRs (3.3%). The rate of death from cSCC per 1000 person-years was 1.7 (95% CI, 1.5-1.8) in non-OTRs and 5.4 (95% CI, 3.9-7.4) in OTRs, with OTRs having a 5.5-fold increased rate in the adjusted analysis. Conclusions and Relevance: In this cohort study, OTRs with cSCC had significantly higher rates of second cSCC, metastasis, and death from cSCC than non-OTRs with cSCC, although most patients with cSCC in both groups died from causes other than cSCC. These findings are relevant for the planning of follow-up of patients with cSCC and for skin cancer services.

A man in his forties with a rash and hallucinations. / En mann i 40-årene med utslett og hallusinasjoner.

Acute exacerbation of rash is common in patients with atopic dermatitis and has diverse aetiology. We describe a patient with atopic dermatitis who developed a pruritic, burning and weeping rash. The rash quickly worsened and developed into a serious condition for which early diagnosis and treatment are crucial.

Teledermatology in Norway using a mobile phone app.

Rashes, ulcers and skin lesions are well suited for telemedicine. We have developed a smartphone app, the first of its kind in Norway, where a referring physician can write a short medical history and take clinical and dermatoscopic photographs with a smartphone, which is then sent to and evaluated by a dermatologist. In the period from June 1st, 2017, to September 1st, 2019, clinical information and photographs of rash and skin lesions from 171 patients were sent by 40 primary care and nursing home physicians via the smartphone app to four dermatologists for diagnosis and therapeutic advice. A wide range of dermatological conditions were diagnosed, most commonly chronic ulcers (17%), eczema (15%) and pigmented lesions (13%). Assessed later by a dermatologist, referral for regular consultations with a specialist was avoided in 119 patients (70%). Sixteen patients (9%) were recommended a regular consultation with a dermatologist; information for prioritization in the specialist healthcare service was then provided. In 36 patients (21%), further measures by the referring physician were recommended. Our experience indicates that many ordinary consultations on rash, ulcers and skin lesions in the specialist healthcare services can be avoided when using the smartphone app.

Management of Cyclosporine-Influenced Gingival Enlargement With Azithromycin.

INTRODUCTION: Management of drug-influenced gingival enlargement is challenging, and surgery is most often indicated. However, because of a unique mechanism of action, azithromycin helps in the management of gingival enlargement caused by cyclosporine. An incidental observation of the effect of azithromycin in the cyclosporine-influenced gingival enlargement by physicians in 1995 led to series of basic investigations and clinical trials confirming this observation and providing a non-surgical treatment modality. CASE PRESENTATION: In this report, successful management of cyclosporine-influenced gingival enlargement in a 39-year-old renal transplant patient with the use of azithromycin without any surgical intervention is presented. CONCLUSION: Use of azithromycin for managing cyclosporine-influenced gingival enlargement is a useful alternative or adjunct to surgical management. It is hoped that this report will raise further awareness of this non-surgical modality in patients taking cyclosporine.

Reporting Quality of Randomized Controlled Trials of Periodontal Diseases in Journal Abstracts-A Cross-sectional Survey and Bibliometric Analysis.

OBJECTIVE: Randomized controlled trials (RCTs) by proper design, conduct, analysis, and reporting provide reliable information in clinical care. Reporting of RCT abstracts is of equal importance as there is evidence that many clinicians will change their clinical decisions based on RCT abstracts. The reporting quality of RCT abstracts has been suboptimal. It is not clear whether the reporting quality is related to the journal metrics. The main objective of this study is to conduct a cross-sectional survey to evaluate the reporting quality of RCTs of periodontal diseases in journal abstracts and to perform a bibliometric analysis. The null hypothesis was that there is no association between the journal metrics (5-year impact factor, Eigenfactor score, and Article Influence Score), abstract metrics (word count, and number of authors), journal endorsement of Consolidated Standards of Reporting Trials (CONSORT), and the overall quality of reporting of CONSORT RCT abstract-modified checklist questions. MATERIALS: CONSORT RCT abstract extension checklist with explanation and elaboration was used and modified to assess the quality of reporting of RCT abstracts of periodontal diseases in the journal abstracts in the year 2012. Bibliometric analysis of journal metrics (5-year impact factor, Eigenfactor score, and Article Influence Score) and abstract metrics (number of authors and abstract word count), the geographic distribution, and the CONSORT-endorsing journal abstracts was compared with the reporting quality of RCT abstracts in periodontal diseases. Calibration and intrarater agreement were done before the data collection and analysis. A second reviewer was consulted for independent evaluation and clarification as needed. For descriptive analysis, the values of continuous variables were expressed as median and interquartile ranges (IQRs) and as proportion percent for binary categorical variables. For association analysis between the binary (yes/no) response variable and the continuous variable, the Mann-Whitney test (for independent samples) was used. For examining the association between 2 categorical variables, Fisher's exact test was used. The chi-square test was performed to examine the association between 2 sets of binary response variables (yes/no). A P value of < .05 was considered statistically significant. All analyses were conducted using SAS, version 9.4. RESULTS: A total of 198 RCT abstracts of periodontal diseases in the year 2012 from 57 journals were included in the study. Fifteen journals, listed as endorsers of CONSORT, contributed 108 RCT abstracts. Four journals (Journal of Periodontology, Journal of Clinical Periodontology, Clinical Oral Implants Research, and European Journal of Oral Implantology) contributed 84 of 198 RCT abstracts in 2012. European countries contributed the majority (n = 81, 40.91%) of RCT abstracts. Among 31 countries in this study, United States contributed the most RCTs (n = 28, 14.14%) followed by India (24, 12.12%), Italy (n = 22, 11.11%), and Brazil (n = 20, 10.1%). The frequency of journal metrics were 5-year impact factor (median 2.316; IQR: 1.439-2.970); Eigenfactor score (0.00474; 0.00202-0.01395); and Article Influence Score (0.553; 0.382-0.755). The number of authors in 198 RCT abstracts ranged between 2 and 20 (median n = 5, IQR: 4-6), whereas the word count ranged between 48 and 569 (median 235, IQR: 205-269). All RCT abstracts reported the experimental interventions (checklist question #5, frequency 100%). Some items were almost always reported-participant eligibility criteria (#3, 99%); comparison interventions (#6, 99.5%); specific objective or hypothesis (#7, 99.5%); primary outcome (#8, 99.5%); and reporting trial results as a summary (#16, 98.5%). All RCT abstracts never reported how the allocations were concealed (#11, 0) and the source of funding for the trials (#23, 0). Some items were almost always never reported-the number of participants included in the analysis for each intervention (#15, 2%); trial registration number (#21, 2.5%); name of trial register (#22, 2.5%); and how the randomization or sequence generation was done (#22). Dismal reporting was noted in many checklist questions including the identification of the study as randomized in the title #1, 51%; design of the trial #2, 32.8%; trial setting #4, 3.5%; randomization #10, 3.5%; blinding #12, 21.7%; details about blinding #13, 8.1%; number of participants randomized to each intervention #14, 26.3%; effect size #17, 13.6%; precision of the estimate of the effect #18, 6.1%; and adverse effects #19, 14.1%. Strikingly, there was a very high reporting of statistical significance #25, 92.4%. European countries, in particular, reported relatively better than other countries in essential questions such as #17 effect size reporting, and #18 precision (uncertainty), which have been largely unreported by rest of the countries. Finally, despite the majority of RCTs published in 2012 were by CONSORT-endorsing journals, there was no difference in the quality of reporting in majority of checklist items when compared with journals not listed as CONSORT endorsers. With few exceptions, there was no statistically significant association between the majority of the CONSORT RCT abstract checklist questions and the journal metrics and abstract metrics analyzed in this study. Unexpectedly, lower ranking journals in journal metrics reported certain essential checklist questions relatively better. CONCLUSION: The reporting quality of RCT of periodontal diseases in the journal abstracts published in 2012 needs substantial improvement. These items have been laid out in this study to help all stakeholders-authors, clinicians, researchers, peer reviewers, journal editors, and publishers to take note and help with the improvement of the same. Despite few significant associations in the bibliometric factors analyzed with better reporting, the results overall led to the failure to reject the null hypothesis that there is no association between the journal metrics, word count, and number of authors and the quality of reporting of CONSORT RCT abstract-modified checklist questions.

Long-term Change in the Risk of Skin Cancer After Organ Transplantation: A Population-Based Nationwide Cohort Study.

Importance: The high risk of skin cancer after organ transplantation is a major clinical challenge and well documented, but reports on temporal trends in the risk of posttransplant cutaneous squamous cell carcinoma (SCC) are few and appear contradictory. Objective: To study temporal trends for the risk of skin cancer, particularly SCC, after organ transplantation. Design, Setting, and Participants: Population-based, nationwide, prospective cohort study of 8026 patients receiving a kidney, heart, lung, or liver transplant in Norway from 1968 through 2012 using patient data linked to a national cancer registry. The study was conducted in a large organ transplantation center that serves the entire Norwegian population of approximately 5.2 million. Exposures: Receiving a solid organ transplant owing to late-stage organ failure, followed by long-term immunosuppressive treatment according to graft-specific treatment protocols. Main Outcomes and Measures: Occurrence of first posttransplant SCC, melanoma, or Kaposi sarcoma of the skin. Risk of skin cancer was analyzed using standardized incidence ratios (SIRs) and, for SCC, multivariable Poisson regression analysis of SIR ratios, adjusting for 5-year time period of transplantation, different follow-up time, age, sex, and type of organ. Results: The study cohort included 8026 organ transplant recipients, 5224 men (65.1%), with a mean age at transplantation of 48.5 years. Median follow-up time was 6.7 years per recipient; total follow-up time, 69 590 person-years. The overall SIRs for SCC, melanoma, and Kaposi sarcoma were 51.9 (95% CI, 48.4-55.5), 2.4 (95% CI, 1.9-3.0), and 54.9 (95% CI, 27.4-98.2), respectively. In those who underwent transplantation in the 1983-1987 period, the unadjusted SIR for SCC was 102.7 (95%, 85.8-122.1), declining to 21.6 (95% CI, 16.8-27.0) in those who underwent transplantation in the 2003-2007 period. Adjusting for different follow-up times and background population risks, as well as age, graft organ, and sex, a decline in the SIR for SCC was found, with SIR peaking in patients who underwent transplantation in the 1983-1987 period and later declining to less than half in patients who underwent transplantation in the 1998-2002, 2003-2007, and 2008-2012 periods, with the relative SIRs being 0.42 (95% CI, 0.32-0.55), 0.31 (95% CI, 0.22-0.42), and 0.44 (95% CI, 0.30-0.66), respectively. Conclusions and Relevance: The risk of SCC after organ transplantation has declined significantly since the mid-1980s in Norway. Less aggressive and more individualized immunosuppressive treatment and close clinical follow-up may explain the decline. Still, the risk of SCC in organ transplant recipients remains much higher than in the general population and should be of continuous concern for dermatologists, transplant physicians, and patients.

Cutaneous head and neck melanoma (CHNM): A population-based study of the prognostic impact of tumor location.

BACKGROUND: Most studies of cutaneous head and neck melanomas (CHNM) have reported poorer survival in CHNM compared with other sites, especially on the scalp/neck. OBJECTIVE: We sought to compare patient and tumor characteristics between CHNM and cutaneous trunk and extremity melanomas and between CHNM locations (face/ear vs scalp/neck, anterior vs posterior), and to study prognostic factors in patients with CHNM. METHODS: We studied all CHNM (n = 1074) from 8120 cases of cutaneous melanomas diagnosed in Norway in 2008 to 2012. RESULTS: Compared with cutaneous trunk and extremity melanomas, CHNM were more frequently found in men, more often nodular and lentigo maligna cutaneous melanomas, and diagnosed at higher T stage (P ≤ .01). CHNM located on posterior sites were diagnosed at significantly higher T stage, and were significantly more often diagnosed with ulceration and at more advanced stage compared with CHNM located on anterior sites (P < .001). T stage and clinical stage were the only significant prognostic factors for melanoma-specific and overall death in the multivariable analysis (P < .001). LIMITATIONS: Low number of cases and the relatively high frequency of missing values are limitations. CONCLUSION: More advanced CHNM were diagnosed on posterior compared with anterior locations, but location was not a significant prognostic factor for cutaneous melanoma-specific or overall death in the multivariable models.

Vitamin D in Norwegian renal transplant recipients: A longitudinal study with repeated measurements in winter and summer.

BACKGROUND: Organ transplant recipients (OTR) have an increased risk of non-melanoma skin cancer (NMSC) and are advised to avoid direct sunlight. OTR living in the Nordic countries are especially vulnerable to hypovitaminosis D as vitamin D production in the skin is restricted to the summer months. OBJECTIVES: To investigate constitutional and external factors predicting hypovitaminosis and seasonal variation of vitamin D in renal transplant recipients (RTR) living in the vicinity of Oslo (59(o) N). METHODS: Ninety-four RTR were included. Interviews covering dietary intake of vitamin D and sun exposure were performed and blood samples were collected in February and August 2013. Results Mean age of patients was 56.8 years and mean graft age 14.5 years. The mean daily total vitamin D intake was 11.8 µg, and the prevalence of hypovitaminosis D (<75 nmol/L) was 67.0% in winter and 56.4% in summer. Sunscreen users had significantly higher 25(OH)D than non-users (p = 0.03). Excluding patients having travelled to southern latitudes during the last three months before blood sampling, no statistical difference was found between winter and summer values of vitamin D (p = 0.60). Being male or having red/light blond hair colour increased vitamin D values significantly from winter to summer. CONCLUSIONS: Hypovitaminosis D is relatively frequent in Norwegian RTR but not as frequent as earlier reported in studies of RTR from lower latitudes. Lack of seasonal variation in vitamin D may be explained by sun protective behaviour and high dietary intake of vitamin D among patients in this study.

Increased expression of monocarboxylate transporter 1 after acute ischemia of isolated, perfused mouse hearts.

AIMS: Lactate is transported by stereo-specific, pH-dependent monocarboxylate transporters (MCTs), of which MCT1 is expressed in abundance in rodent and human hearts. This study investigated the expression and functional role of MCT1 in mouse hearts during acute myocardial ischemia. MAIN METHODS: Mice hearts were isolated and Langendorff-perfused with induced global ischemia (40 min) and reperfusion with function and infarct size as end-points. Hearts were collected serially for protein extraction and immunoblotting with an MCT1 antibody, and for determining subcellular localization with immunogold EM. Immortalized cardiomyocytes (HL-1 cells) were injured with hydrogen peroxide, and cell death in the presence or absence of the competitive inhibitor of MCT1, d-lactate, was evaluated by Trypan blue exclusion. KEY FINDINGS: MCT1 expression increased after 15 min reperfusion (p<0.05), but was not significantly increased after 60 min. MCT1 was localized in mitochondria, plasma membrane, and intercalated disks. At 15 min reperfusion, gold particle count was increased in the intercalated disks (p<0.05). d-lactate administration to isolated hearts either for 5 min before ischemia or at the first 5 min of reperfusion increased infarct size (p<0.01). A significant impairment of left ventricular performance was found when d-lactate was given before ischemia. MCT1 expression was not influenced by d-lactate. When HL-1 cells were treated with d-lactate before injury was induced with hydrogen peroxide, cell death was increased (p<0.05). SIGNIFICANCE: Inhibition of MCT1 increases cell death. Increased MCT1 expression after ischemia and reperfusion is likely to restore cardiac pH through lactate export.

Postconditioning in rats and mice.

OBJECTIVE: For subsequent studies on the molecular mechanisms of postconditioning, we aimed to identify a robust postconditioning protocol in rat and mouse heart. DESIGN: Isolated rat hearts were subjected to different postconditioning protocols (study 1 and 2). The protection was compared to preconditioning. Rats (study 3) in vivo in two different laboratories were postconditioned. Isolated mouse hearts (study 4) and mice in vivo (study 5) were postconditioned. RESULTS: Postconditioning did not protect isolated, perfused rat hearts, however, preconditioning improved function and reduced infarct size. Postconditioning tended to protect rat hearts in vivo in one laboratory (p = 0.10), whereas protection was seen in the other laboratory (infarct size 51+/-11% vs controls 62+/-3%, p = 0.01). Postconditioned mouse hearts were protected, both ex vivo (16+/-9% vs controls 33+/-18%, p = 0.02) and in vivo (21+/-5% vs 42+/-7%, p < 0.001). CONCLUSIONS: Rat hearts are less suitable for studies of mechanisms of postconditioning. The results suggest that the signaling pathways differ between pre- and postconditioning. Mouse hearts were strongly protected by postconditioning, and genetically engineered mice may be useful for postconditioning research.