Evaluation of primary care physicians' competence in selective skin tumour triage after short versus long dermoscopy training: a randomized non-inferiority trial.

BACKGROUND: Although primary care physicians (PCPs) play a key role in skin cancer screening, their skills in detecting malignant tumours is suboptimal. OBJECTIVES: To determine whether a short dermoscopy e-learning course (4 h) in skin tumour diagnosis for PCPs is non-inferior to a long course (12 h) in selective triage of skin lesions. Secondly, to evaluate whether regular refresher training sessions are necessary to maintain the PCPs' skills in the medium term. METHODS: A randomized 2 × 2 factorial non-inferiority trial was conducted online over an 8-month period among 233 PCPs including 126 certified general practitioners, 94 PCPs in training, and 13 occupational physicians, all without prior advanced dermoscopy training. Participants were randomized 1:1:1:1 to receive short training and mandatory refreshers (n = 58), short training and optional refreshers (n = 59), long training and mandatory refreshers (n = 58), or long training and optional refreshers (n = 58). PCPs' skills were evaluated before training (T0), immediately after training (T1) to test the non-inferiority, and after 5 months (T2) to evaluate the impact of the refreshers. The primary endpoint was the difference in the change of score after short and long training. The non-inferiority margin was set at -28%. RESULTS: Among the 233 randomized participants, 216 (93%) completed T1 and 197 (84.5%) completed T2. For short versus long training, the primary endpoint was 1.392 (95% CI: 0.138; 2.645) in the per-protocol population (p < 0.001) and 1.016 (95% CI: -0.224; 2.256) in the modified intention-to-treat population (p < 0.001). After training, the type of refresher showed no impact on the score (p = 0.840). However, PCPs who completed all refreshers showed the best mean overall score at T2 (p < 0.001). CONCLUSIONS: These findings confirm that short dermoscopy e-learning is non-inferior in training PCPs to triage skin lesions compared to long training. After training, regular refreshers are important to maintain the PCPs' acquired skills over time.

A simple nomogram for early postoperative risk prediction of clinically relevant pancreatic fistula after pancreatoduodenectomy.

PURPOSE: Postoperative pancreatic fistulae (POPF) present a serious and life-threatening complication after pancreatic head resections (PD). Therefore, reliable risk stratification to identify those at risk is urgently needed. The aim of this study was to identify postoperative laboratory parameters for the prediction of POPF in the early postoperative period. METHODS: One hundred eighty-two patients who underwent PD from 2012 until 2017 were retrospectively analyzed. Multivariate logistic regression was performed using the GLM (general linear model) method for model building. Two nomograms were created based on the GLM models of postoperative day one and postoperative day one to five. A cohort of 48 patients operated between 2018 and 2019 served as internal validation. RESULTS: Clinically relevant pancreatic fistulae (CR-POPF) were present in 16% (n = 29) of patients. Patients with CR-POPF experienced significantly more insufficiencies of gastroenterostomies, delayed gastric emptying, and more extraluminal bleeding than patients without CR-POPF. Multivariate analysis revealed multiple postoperative predictive models, the best one including ASA, main pancreatic duct diameter, operation time, and serum lipase as well as leucocytes on day one. This model was able to predict CR-POPF with an accuracy of 90% and an AUC of 0.903. Two nomograms were created for easier use. CONCLUSION: Clinically relevant fistula can be predicted using simple laboratory and clinical parameters. Not serum amylase, but serum lipase is an independent predictor of CR-POPF. Our simple nomograms may help in the identification of patients for early postoperative interventions.

Self-reported body silhouettes: a diagnostic instrument for anthropometric parameters.

OBJECTIVE: Routine body size measurement of anthropometric values requires professionals, standardized techniques, and calibrated tools. Therefore, there is a need for easier screening tools such as the self-reported body silhouette (Self-bosi). The aim of this study was to analyze the performance of Self-bosi as a proxy of anthropometric values. STUDY DESIGN: Prospective analytic study of the Health Workers Cohort Study. METHODS: Adult participants of the Health Workers Cohort Study were included. Then, through the calculation sensitivity and specificity of Self-bosi to detect abnormal waist circumference (WC) (≥90 cm for male and ≥80 cm for female participants), elevated body fat percentage (BF%) (≥25% for male and ≥35% for female participants), as well as overweight and obesity (≥25 kg/m2) and obesity (≥30 kg/m2). RESULTS: A total of 2471 male and 5940 female participants were analyzed. Overall, Self-bosi discriminate high WC values (area under the curve [AUC]; male participants: 0.80, female participants: 0.82); increased BF% (AUC: male participants: 0.78, female participants: 0.83); overweight and obesity (AUC: male participants: 0.81, female participants: 0.86); and obesity (AUC: male participants: 0.83, female participants: 0.89). CONCLUSION: Self-bosi is an accurate method to assess increased WC, BF%, obesity, and overweight-obesity in Mexican adults. Given its simplicity and low-cost of the self-reported body silhouette, it might be considered a useful anthropometric screening instrument in large scale epidemiological research.

Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society.

BACKGROUND: Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. OBJECTIVES: We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non-neoplastic dermatoses through an expert consensus. METHODS: The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three-step iterative procedure (blinded e-mail interaction in rounds 1 and 3 and a face-to-face meeting in round 2). Initial panellists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses. RESULTS: Twenty-four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) 'other structures' (including colour and morphology); and (v) 'specific clues'. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure). CONCLUSIONS: This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology. What's already known about this topic? Over the last few years, several papers have been published attempting to describe the dermoscopic features of non-neoplastic dermatoses, yet there is poor consistency in the terminology among different studies. What does this study add? The present expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This consensus should enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.

Human surface anatomy terminology for dermatology: a Delphi consensus from the International Skin Imaging Collaboration.

BACKGROUND: There is no internationally vetted set of anatomic terms to describe human surface anatomy. OBJECTIVE: To establish expert consensus on a standardized set of terms that describe clinically relevant human surface anatomy. METHODS: We conducted a Delphi consensus on surface anatomy terminology between July 2017 and July 2019. The initial survey included 385 anatomic terms, organized in seven levels of hierarchy. If agreement exceeded the 75% established threshold, the term was considered 'accepted' and included in the final list. Terms added by the participants were passed on to the next round of consensus. Terms with <75% agreement were included in subsequent surveys along with alternative terms proposed by participants until agreement was reached on all terms. RESULTS: The Delphi included 21 participants. We found consensus (≥75% agreement) on 361/385 (93.8%) terms and eliminated one term in the first round. Of 49 new terms suggested by participants, 45 were added via consensus. To adjust for a recently published International Classification of Diseases-Surface Topography list of terms, a third survey including 111 discrepant terms was sent to participants. Finally, a total of 513 terms reached agreement via the Delphi method. CONCLUSIONS: We have established a set of 513 clinically relevant terms for denoting human surface anatomy, towards the use of standardized terminology in dermatologic documentation.

Dermatoscopic features of thin (≤2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society.

BACKGROUND: Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour. OBJECTIVE: To investigate the dermatoscopic morphology of thin (≤2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours. METHODS: Retrospective, morphological case-control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed. RESULTS: Overall, 254 tumours were collected (69 NM of Breslow thickness ≤2 mm, 96 NM >2 mm and 89 non-melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in ≤2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4-fold), white shiny streaks (2.9-fold) and irregular blue structureless area (2.4-fold) were predictors for thinner NM compared to non-melanoma nodular tumours. Overall, irregular blue structureless area (3.4-fold), dotted vessels (4.6-fold) and serpentine vessels (1.9-fold) were predictors of all NM compared to non-melanoma nodular lesions. LIMITATIONS: Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community. CONCLUSIONS: Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non-melanoma nodular tumours.

Dynamics of Fluorescent Imaging for Rapid Tear Thinning.

A previous mathematical model has successfully simulated the rapid tear thinning caused by glob (thicker lipid) in the lipid layer. It captured a fast spreading of polar lipid and a corresponding strong tangential flow in the aqueous layer. With the simulated strong tangential flow, we now extend the model by adding equations for conservation of solutes, for osmolarity and fluorescein, in order to study their dynamics. We then compare our computed results for the resulting intensity distribution with fluorescence experiments on the tear film. We conclude that in rapid thinning, the fluorescent intensity can linearly approximate the tear film thickness well, when the initial fluorescein concentration is small. Thus, a dilute fluorescein is recommended for visualizing the rapid tear thinning during fluorescent imaging.

[Dermoscopy in special locations : Nails, acral skin, face, and mucosa]. / Dermatoskopie in Sonderlokalisationen : Nägel, akrale Haut, Gesicht und Mukosa.

The use of dermoscopy by dermatologists across Europe has become a standard examination for benign and malignant skin lesions and increasingly also for inflammatory skin diseases. However, based on the experience of the authors from numerous dermoscopy courses, knowledge about important dermoscopic features in special locations such as mucosa or nails is often limited. This may be explained by (1) a different anatomy of the skin and its adnexa in special locations in comparison to the remaining integument, (2) difficult technical access to special locations with a dermatoscope, and (3) a rather low incidence of malignant skin neoplasms in areas of special locations (with the exception of facial skin/scalp). This article aims at explaining dermoscopic characteristics and features of important benign and malignant lesions of nails, acral skin, face, and mucosa.

[Advanced medical post within hospitals as possible tactical instrument for handling mass casualty incidents]. / Der Behandlungsplatz innerhalb eines Krankenhauses als mögliches taktisches Werkzeug zur Bewältigung eines Massenanfalls von Patienten.

BACKGROUND: An important instrument for handling mass casualty incidents in preclinical settings is the use of an advanced medical post. In certain circumstances, however, the establishment of such an advanced medical post on or close to the incident site is impossible. Terrorist attacks are a prime example for this. The highest priority for hospitals during mass casualty incidents is to adjust the treatment capacity to the acute rise in demand and to sustain its functionality throughout the duration of the incident. By establishing an advanced medical post within hospitals during certain types of mass casualty incidents these aims could potentially be accomplished. AIMS: The aims of this pilot study were to test the practicability of the establishment of an advanced medical post within a university hospital and to identify potential problems. The results provide the foundation of a generalized concept, which will then be integrated into the hospital emergency plans. METHODS: After the formation of a multiprofessional expert committee, different areas within the hospital were evaluated based on spatial and tactical considerations. Predefined questions were assessed and harmonized with respect to organization, vehicle management, communication, leadership and patient transport through the means of a practice run. RESULTS: The establishment and operation of an advanced medical post within the hospital were easily possible. The consequent deployment of section leaders enabled the smooth coordination of transport and an unobstructed simulated patient flow. The management of the treatment area by a senior emergency physician and a senior emergency medical service officer in close cooperation with the operational hospital lead proved to be a useful concept. Technical problems with communication within the hospital were resolved by using wireless phones and the installation of a digital radio repeater. DISCUSSION: During acute scenarios with only short prior notice, the authors prefer concepts that supplement the normal hospital operation through additional staff and material. In circumstances with prior notice of more than 60 min an advanced intrahospital advanced medical post, staffed by civil protection units, could be a concept that enables the absorption of the first patient arrivals within the first hour of a mass casualty incident without disturbing the functionality of hospitals to any great extent. Further practice runs are, however, necessary to further develop and adjust this concept to real-life circumstances.

Dermoscopy and the diagnosis of primary cutaneous B-cell lymphoma.

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCLs) are frequently misdiagnosed, and a biopsy is needed to attain the correct diagnosis. OBJECTIVE: To characterize the dermoscopic features of PCBCL. METHODS: In this retrospective observational study, we analysed the pathology reports of 172 newly diagnosed PCBCL for the initial clinical differential diagnosis. The dermoscopic images of 58 PCBCL were evaluated for dermoscopic features. Two dermoscopy experts, who were blinded to the diagnosis and the study objective, evaluated images from 17 cases for a dermoscopic differential diagnosis. RESULTS: Of 172 biopsy-proven PCBCL lesions, cutaneous lymphoma was suspected by the clinician in 16.3%; the leading diagnosis was basal cell carcinoma in 17.4%, and other skin neoplasms in 21%. Studying 58 PCBCL dermoscopic images, we most frequently identified salmon-coloured background/area (79.3%) and prominent blood vessels (77.6%), mostly of serpentine (linear-irregular) morphology (67.2%). Dermoscopic features did not differ significantly by subtype or location. Blinded evaluation by dermoscopy experts raised a wide differential diagnosis including PCBCL, arthropod bite, basal cell carcinoma, amelanotic melanoma and scar/keloid. CONCLUSIONS: Two dermoscopic features, salmon-coloured area/background and serpentine vessels, are frequently seen in PCBCL lesions. These characteristic dermoscopic features, although not specific, can suggest a possible diagnosis of PCBCL.

Duplex Tear Film Evaporation Analysis.

Tear film thinning, hyperosmolarity, and breakup can cause irritation and damage to the human eye, and these form an area of active investigation for dry eye syndrome research. Recent research demonstrates that deficiencies in the lipid layer may cause locally increased evaporation, inducing conditions for breakup. In this paper, we explore the conditions for tear film breakup by considering a model for tear film dynamics with two mobile fluid layers, the aqueous and lipid layers. In addition, we include the effects of osmosis, evaporation as modified by the lipid, and the polar portion of the lipid layer. We solve the system numerically for reasonable parameter values and initial conditions and analyze how shifts in these cause changes to the system's dynamics.

[Dermoscopy for malignant and benign skin tumors : Indication and standardized terminology]. / Dermatoskopie bei malignen und benignen Hauttumoren : Indikation und standardisierte Terminologie.

Dermoscopy has a high diagnostic accuracy in pigmented and nonpigmented malignant and benign skin tumors. These microscopic in vivo examinations with polarized and nonpolarized light are effective in the early detection of malignant skin tumors and reduce the number of unnecessary excisions of benign skin tumors. The selection of the skin lesions is crucial for the diagnostic accuracy of the dermoscopic examination. Not only large pigmented skin lesions, but also small hypo-, de-, or nonpigmented skin lesions, should be examined dermatoscopically as well as skin lesions that have changed in shape and/or color. In clinical routine, research and teaching, the dermoscopic diagnosis should be performed by describing the visible structures, their distribution and colors by means of descriptive and/or metaphoric terminology. Optionally, a diagnostic algorithm can also be used. Especially in benign lesions, the dermatoscopic diagnosis should be uniform for the complete area. Comparison with other nearby skin tumors of the same patient (comparative approach) is helpful in the evaluation of numerous melanocytic skin tumors. If it is unclear whether the lesion is malignant, a biopsy or complete excision should be performed with subsequent histopathological examination.

Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status.

BACKGROUND: Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear. OBJECTIVES: To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers. METHODS: In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild-type (BRAFwt) melanoma at the time of first distant metastasis. RESULTS: In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P = 0·01) and significantly higher (P = 0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P < 0·01). In BRAFm melanoma, elevated S100B levels showed no prognostic influence (P = 0·18). Elevated lactate dehydrogenase (LDH) levels had a significantly negative impact on mOS in both groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared with BRAFm patients not receiving BRAFi (P = 0·01). No difference in mOS between BRAFm patients who did not receive BRAFi treatment and BRAFwt patients was observed. CONCLUSIONS: Better mOS was observed in BRAFm patients treated with BRAFi. BRAFm patients not treated with BRAFi show similar survival curves to BRAFwt patients. Elevated LDH is a BRAF-independent prognostic parameter; S100B has prognostic significance in BRAFwt melanoma only.

A cost-effectiveness analysis of trametinib plus dabrafenib as first-line therapy for metastatic BRAF V600-mutated melanoma in the Swiss setting.

BACKGROUND: The treatment of patients with metastatic melanomas that harbour BRAF V600E or V600K mutations with trametinib plus dabrafenib appears to be superior to treatment with vemurafenib alone. This treatment regimen is likely to become available in Switzerland in the near future. OBJECTIVES: To determine the cost-effectiveness of trametinib plus dabrafenib. METHODS: A Markov cohort simulation was conducted to model the clinical course of typical patients with metastatic melanoma. Information on response rates, clinical condition and follow-up treatments were derived and transition probabilities estimated based on the results of a clinical trial that compared treatment with trametinib plus dabrafenib vs. vemurafenib alone. RESULTS: Treatment with trametinib plus dabrafenib was estimated to cost an additional CHF199 647 (Swiss francs) on average and yield a gain of 0·52 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of CHF385 603 per QALY. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of CHF100 000 per QALY would not be reached at the current US price of trametinib. CONCLUSIONS: The introduction of trametinib in Switzerland at US market prices for the treatment of metastatic BRAF V600-mutated melanoma with trametinib plus dabrafenib is unlikely to be cost-effective compared with vemurafenib monotherapy. A reduction in the total price of the combination therapy is required to achieve an acceptable cost-effectiveness ratio for this clinically promising treatment.

Spectophotometric intracutaneous analysis: an investigation on photodamaged skin of immunocompromised patients.

BACKGROUND: SIAscopy (Spectrophotometric Intracutaneous Analysis) enables non-invasive analysis of the skin. OBJECTIVE: We wanted to determine whether SIAscopy is able to detect and differentiate the skin chromophores melanin, collagen and haemoglobin and the influence of immunosuppressive drugs and other known risk factors for non-melanoma skin cancer (NMSC). METHODS: Volunteers and patients were measured by SIAscopy at six spots on sun-exposed and two spots on sun-protected skin. Measurements were transformed by SIAmetrics into arbitrary units and statistically analysed. RESULTS: Melanin was shown to be higher with age (+1.73759 a.u.; P < 0.0001), sun exposure (+47.03998 a.u.; P < 0.0001), immunosuppression (+10.48526 a.u.; P < 0.0001) and lower in males (-26.50952 a.u.; P < 0.0001). Collagen was lower with increasing age (-0.29162 a.u.; P < 0.0001) and sun exposure (-6.85586 a.u.; P < 0.0001) but higher with male sex (+8.34251 a.u.; P < 0.0001) and immunosuppression (+5.79171 a.u.; P = 0.0001). Haemoglobin was lower with increasing age (-0.23833 a.u.; P = 0.0005), but higher with male sex (+18.51976 a.u.; P < 0.0001) and sun exposure (+13.74523 a.u.; P < 0.0001). Haemoglobin content was not associated to immunosuppression. CONCLUSION: Our results encourage the use of SIAscopy as a tool to better gauge an individual patient's NMSC risk factors. Further studies should help to better delineate SIAscopy as a prognostic tool.

A multifaceted intervention: no increase in general practitioners' competence to diagnose skin cancer (minSKIN) - randomized controlled trial.

BACKGROUND: General practitioners (GPs) play crucial roles in early detection of skin cancer. A pilot-study found a positive short-term effect of a 1-day dermatologic education programme on GPs' diagnostic competence. OBJECTIVE: To determine effects of a multifaceted intervention, including technical equipment and continuing feedback by a dermatologist, on GPs' diagnostic skills regarding skin cancer. METHODS: Randomized controlled trial with 78 GPs of the Canton of Zurich, Switzerland. INTERVENTION: GPs in intervention group received a 1-day training, a Lumio (magnifying glass with polarized light, 3Gen), a Nikon digital camera and - during 1 year - feedback on skin lesion pictures sent to the dermatologist. GPs in control group only received the 1-day training. PRIMARY OUTCOME: structured assessment of GP's diagnostic skills in correctly diagnosing images of skin lesions regarding skin cancer. At baseline prior to intervention (T0), after the full-day training course in both groups (T1), and after 1 year of continuing feedback (T2) to the intervention group. MEASURES: Non-parametric unpaired (Wilcoxon-Mann-Whitney) tests were used to compare numbers of correctly classified skin lesions between both groups at T2 and for the change between T1 and T2. RESULTS: At T0, both groups classified a median of 23 skin lesions of the 36 images correctly. This value rose to 28 for both groups at T1 and fell to 24 for both groups at T2. No difference between control and intervention group at T2. Furthermore, we compared differences in the sum scores per GP between T1 and T2 for each group. Also in this comparison, no difference between control and intervention group was found. CONCLUSION AND RELEVANCE: No long-term effect of the multifaceted intervention was found on the competence to diagnose skin cancer by GPs. The positive short-term effect of the 1-day dermatologic education programme did not persist over 12 months.

Tld1 is a regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation.

Cells store lipids in the form of triglyceride (TG) and sterol ester (SE) in lipid droplets (LDs). Distinct pools of LDs exist, but a pervasive question is how proteins localize to and convey functions to LD subsets. Here, we show that the yeast protein YDR275W/Tld1 (for TG-associated LD protein 1) localizes to a subset of TG-containing LDs and reveal it negatively regulates lipolysis. Mechanistically, Tld1 LD targeting requires TG, and it is mediated by two distinct hydrophobic regions (HRs). Molecular dynamics simulations reveal that Tld1's HRs interact with TG on LDs and adopt specific conformations on TG-rich LDs versus SE-rich LDs in yeast and human cells. Tld1-deficient yeast display no defect in LD biogenesis but exhibit elevated TG lipolysis dependent on lipase Tgl3. Remarkably, overexpression of Tld1, but not LD protein Pln1/Pet10, promotes TG accumulation without altering SE pools. Finally, we find that Tld1-deficient cells display altered LD mobilization during extended yeast starvation. We propose that Tld1 senses TG-rich LDs and regulates lipolysis on LD subpopulations.