Not all that glitters is COVID-19: a case series demonstrating the need for histopathology when skin findings accompany SARS-CoV-2 infection.

BACKGROUND: Descriptions of cutaneous findings associated with COVID-19 have not been consistently accompanied by histopathology or confirmatory testing for SARS-CoV-2. OBJECTIVE: To describe and classify the cutaneous findings with supporting histopathology of confirmed COVID-19 inpatients. METHODS: We included consecutive inpatients with a confirmed diagnosis of COVID-19 for whom a dermatology consult was requested. A skin biopsy was performed in all cases. Skin findings were classified as being compatible with a cutaneous manifestation of COVID-19 or as representing a distinct clinical entity. RESULTS: Twenty-eight patients were studied in whom thirty-one dermatologic diagnoses were made. Twenty-two of the dermatoses were compatible with a cutaneous manifestation of COVID-19; nine entities were not associated with infection by SARS-CoV-2. The most common COVID-19-associated pattern was an exanthematous presentation. In four patients, a new pattern was observed, characterized by discrete papules with varied histopathological findings including a case of neutrophilic eccrine hidradenitis. No cases of pernio-like lesions were identified. Skin findings not associated with COVID-19 represented 29% of diagnoses and included Malassezia folliculitis, tinea, miliaria and contact dermatitis. LIMITATIONS: There is no gold-standard test to distinguish between viral exanthems and drug reactions. CONCLUSION: A histopathological study is critical before attributing skin findings to a manifestation of COVID-19.

A low-cost towed video camera system for underwater surveys: comparative performance with standard methodology.

Technological advances in the field of underwater video have led to an exponential increase in the use of drifting cameras (DC) and remotely operated vehicles (ROVs) to monitor the diversity, abundance, and size structure of marine life. Main advantages of DCs relative to ROVs are their lower costs and the much simpler logistics required to operate them. This study compares the performance of a new low-cost DC system equipped with a novel measuring device with that of a standard DC bearing an array of laser pointers. The new DC, which can be operated from a small boat, carries a pair of parallel steel "whiskers" that are dragged on the seabed within the field of view of the camera, providing a scale for measuring and estimating the density of benthic biota. An experiment conducted using an array of objects of known sizes laid on the bottom showed that its performance in terms of both size and density estimation was similar to that of the standard technique based on laser pointers. Measurement errors had a negligible negative bias (- 2.3%) and a standard deviation that ranged between 13 and 8% for objects from 25 to 110 mm in size. The whiskers offered a simplified method for density estimation that avoids the need to calculate the width of the field of view, thus reducing the video processing time by around 60% with respect to the standard method. Briefly, the new system offers an efficient low-cost alternative for benthic ecology studies conducted on soft or non-irregular bottoms.

Oral anticoagulation with vitamin K inhibitors and determinants of successful self-management in primary care.

BACKGROUND: Self-management may be an option to monitor oral anticoagulant therapy in health systems, but before recommending it, we need to assess patients' ability to take on this task. The purpose of the study was to describe patients' ability to self-manage and associated factors. METHODS: This was a 3-year prospective quasi-experimental study with a control group. Overall, 333 patients on anticoagulant therapy from seven primary care health centres of the Basque Health Service were included in the intervention group and followed up for 6 months after the intervention, assessing their ability to self-test and self-manage. The intervention consisted of a patient training programme, providing detailed information on their condition and its treatment, and practical training in how to use a portable blood coagulation monitor and adjust their anticoagulant dose. Comparisons were made with a control group (333 patients receiving OAT under usual care from the same seven health centres). Outcome variables were ability to self-manage, quality of the outcome (in terms of time in therapeutic range), and quality of life in the intervention group, and general patient characteristics (age and sex), clinical variables (reason for OAT, INR range), and quality of the outcome (in terms of percentage of INR measurements in range and complications) in both groups. RESULTS: Overall, 26.13 % of patients invited to participate in the intervention agreed. Of these, 99 % successfully learned to self-manage their OAT. Just 4.2 % did not complete the follow-up, in all cases for reasons unrelated to self-management, and 4.5 % required additional learning support. Outcomes were better than under usual care in terms of percentage of INR measurements in range (12 %), rate of complications (4 %) and quality of life (9.2 %). LIMITATIONS: Patients were only followed-up period for 6 months and the study was conducted in a single health organization. Though patients eligible to participate were selected randomly, they were not randomly allocated to the groups. This is a potential source of selection bias. Data needed to calculate in-range time were not collected from controls; rather the results for the self-management group were compared with external data from other studies. CONCLUSIONS: Almost all participants achieved competency in self-management, with no differences by age, sex, concurrent illnesses, polypharmacy or educational level. The greatest barrier to self-management was the attitude of patients themselves and those around them. Self-management in primary care is a good alternative to usual care, patients having longer times in therapeutic range and fewer complications, and improving their quality of life. Remote management is a good support tool. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01878539.

Estimating tissue-specific discrimination factors and turnover rates of stable isotopes of nitrogen and carbon in the smallnose fanskate Sympterygia bonapartii (Rajidae).

This study aimed to estimate trophic discrimination factors (TDFs) and metabolic turnover rates of nitrogen and carbon stable isotopes in blood and muscle of the smallnose fanskate Sympterygia bonapartii by feeding six adult individuals, maintained in captivity, with a constant diet for 365 days. TDFs were estimated as the difference between δ(13) C or δ(15) N values of the food and the tissues of S. bonapartii after they had reached equilibrium with their diet. The duration of the experiment was enough to reach the equilibrium condition in blood for both elements (estimated time to reach 95% of turnover: C t95%blood = 150 days, N t95%blood = 290 days), whilst turnover rates could not be estimated for muscle because of variation among samples. Estimates of Δ(13) C and Δ(15) N values in blood and muscle using all individuals were Δ(13) Cblood = 1·7‰, Δ(13) Cmuscle = 1·3‰, Δ(15) Nblood = 2·5‰ and Δ(15) Nmuscle = 1·5‰, but there was evidence of differences of c.0·4‰ in the Δ(13) C values between sexes. The present values for TDFs and turnover rates constitute the first evidence for dietary switching in batoids based on long-term controlled feeding experiments. Overall, the results showed that S. bonapartii has relatively low turnover rates and isotopic measurements would not track seasonal movements adequately. The estimated Δ(13) C values in S. bonapartii blood and muscle were similar to previous estimations for elasmobranchs and to generally accepted values in bony fishes (Δ(13) C = 1·5‰). For Δ(15) N, the results were similar to published reports for blood but smaller than reports for muscle and notably smaller than the typical values used to estimate trophic position (Δ(15) N c. 3·4‰). Thus, trophic position estimations for elasmobranchs based on typical Δ(15) N values could lead to underestimates of actual trophic positions. Finally, the evidence of differences in TDFs between sexes reveals a need for more targeted research.

A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with unresectable, nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN). This randomized, open-label, phase III clinical trial compared the efficacy between standard CCRT and two different induction chemotherapy (ICT) regimens followed by CCRT. PATIENTS AND METHODS: Patients with untreated LASCCHN were randomly assigned to ICT (three cycles), with either docetaxel (Taxotere), cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CCRT [7 weeks of radiotherapy (RT) with cisplatin 100 mg/m(2) on days 1, 22 and 43]; or 7 weeks of CCRT alone. The primary end points were progression-free survival (PFS) and time-to-treatment failure (TTF). RESULTS: In the intention-to-treat (ITT) population (n = 439), the median PFS times were 14.6 (95% CI, 11.6-20.4), 14.3 (95% CI, 11.8-19.3) and 13.8 months (95% CI, 11.0-17.5) at TPF-CCRT, PF-CCRT and CCRT arms, respectively (log-rank P = 0.56). The median TTF were 7.9 (95% CI, 5.9-11.8), 7.9 (95% CI, 6.5-11.8) and 8.2 months (95% CI, 6.7-12.6) for TPF-CCRT, PF-CCRT and CCRT alone, respectively (log-rank P = 0.90). There were no statistically significant differences for overall survival (OS). Toxic effects from ICT-CCRT were manageable. CONCLUSION: Overall, this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN.

Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck.

BACKGROUND: The efficacy and safety of a novel combination of weekly paclitaxel and the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab for the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck were investigated. PATIENTS AND METHODS: Patients received paclitaxel (80 mg/m(2)) and cetuximab (400/250 mg/m(2)), weekly, until disease progression or unacceptable toxicity. The primary end point was response rate. RESULTS: Among 46 patients enrolled, the overall response rate was 54% [95% confidence interval (CI) 39% to 69%], with 10 (22%) complete responses and a disease control rate of 80%. Median progression-free and overall survival times were 4.2 (95% CI 2.9-5.5 months) and 8.1 months (95% CI 6.6-9.6 months), respectively. Common grade 3/4 adverse events were acne-like rash (24%), asthenia (17%) and neutropenia (13%). Prior chemotherapy and the development of acne-like rash were associated with tumor response but not survival. No association between tumor EGFR expression or EGFR gene copy number and response or survival was found. CONCLUSION: The combination of cetuximab and weekly paclitaxel was active and well tolerated by these poor prognosis patients and may be an option for the treatment of medically unfit patients, particularly those for whom platinum is contraindicated.

Phase II open-label study of erlotinib in combination with gemcitabine in unresectable and/or metastatic adenocarcinoma of the pancreas: relationship between skin rash and survival (Pantar study).

BACKGROUND: Skin rash is an adverse event which might be associated with longer survival in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors. The aim of this nonrandomised phase II clinical trial is to prospectively evaluate the relationship between skin rash and overall survival (OS) in advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine. PATIENTS AND METHODS: Patients were given gemcitabine (1000 mg/m2/week, 3 weeks every 4 weeks) plus erlotinib (100 mg/day orally continuously) until disease progression/unacceptable toxicity. The primary end point was OS. RESULTS: A total of 153 eligible patients were enrolled (grade≥2 rash, 25%; grade<2 rash, 75%). OS was longer in patients with grade≥2 rash versus grade<2 (11 versus 5 months; P<0.001). Progression-free survival was longer in patients with grade≥2 rash versus grade<2 (6 versus 3 months; P<0.001) and shorter in those without rash versus grade 1 (2 versus 4 months; P=0.005) or grade≥2 (2 versus 6 months; P<0.001). Patients with grade≥2 rash showed higher rates of overall response (21% versus 7%; P<0.05) and disease control (84% versus 43%; P<0.05) versus grade<2. CONCLUSIONS: This study prospectively confirms the relationship between rash and longer OS in unresectable locally advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.

Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment.

BACKGROUND: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. METHODS: Patients aged 18-75 years, with Eastern Cooperative Oncology Group performance status 0-2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m(-2) BID) was administered on days 1-14 every 21 days for at least two cycles. RESULTS: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1-9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). CONCLUSIONS: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules.

Consensus on the treatment of pancreatic cancer in Spain.

Pancreatic cancer (PC) represents one of the greatest oncological challenges of our century, due to its high mortality and incidence. A group of Spanish experts in PC treatment reviewed data available on different therapeutic combinations and established consensus on what would be the best strategy in PC management, depending on the stage of the disease. Surgery with complete resection may produce 5-year survival rates of 18-24%, but definitive control is still precarious. In the absence of consensus, the best evidence suggests that adjuvant chemotherapy with gemcitabine for 6 months using the CONKO-001 regime is the treatment of choice after resection of PC for patients with acceptable functional status. This group recommends chemoradiotherapy (CT-RT) in patients with factors for poor loco-regional prognosis. However, chemotherapy is an option for the treatment of locally advanced PC in patients with good general status and in the absence of metastatic disease the recommended treatment is CT-RT followed by gemcitabine-based chemotherapy. A period of chemotherapy followed by consolidation CT-RT may be appropriate, as it allows selection of patients with locally advanced disease who may benefit most from combined treatment. Erlotinib combined with gemcitabine shows significant survival improvement in PC and must be considered an option in the first-line treatment of advanced and metastatic PC. The gemcitabine-erlotinib combination is proposed as the standard treatment for metastatic PC in patients with PS=/>2. In patients with PS<2, gemcitabine-erlotinib is recommended as the first-line treatment option, supported by a maximum degree of evidence, without ruling out other options, such as gemcitabine-oxaliplatin, gemcitabine-capecitabine or gemcitabine alone.

Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-The ETOP NICOLAS trial.

OBJECTIVES: Chemo-radiotherapy (CRT) and concurrent PD-1 inhibition has shown promising results in pre-clinical models. So far, the feasibility of delivering concurrent CRT and PD-1/PD-L1 inhibition has never been assessed in a clinical trial. MATERIAL AND METHODS: NICOLAS is a phase-II trial evaluating the safety and efficacy of nivolumab combined with CRT in stage III NSCLC. Patients received 3 cycles of platinum-based chemotherapy and concurrent RT (66 Gy/33fractions). Nivolumab started concurrently with RT. The primary endpoint was 6-month post-RT rate of grade-≥3-pneumonitis. A formal interim safety analysis (IA) was scheduled when the first 21 patients reached 3 months follow-up post-RT. An early positive safety conclusion would be reached at IA if there were no grade ≥3-pneumonitis in those patients. Efficacy evaluation was planned provided the safety conclusion was reached. RESULTS AND CONCLUSION: As of 13 December 2018, 82 patients were recruited with median follow-up of 13.4 months. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. For the first 21 patients, no grade-≥3-pneumonitis was observed by the end of the 3-month post-RT follow-up period. The early safety IA provides evidence that the addition of nivolumab to concurrent CRT is safe and tolerable regarding the 6-month rate of pneumonitis grade ≥3 at the one-sided significance level of 5%. Following that, the 1-year progression-free survival will be evaluated in an expanded patient cohort. NICOLAS trial creates the opportunity for assessing the activity of the combination of checkpoint with concurrent CRT in larger prospective trials for locally advanced NSCLC.

Sources of enterococci in Idiazábal-type cheese.

Enterococci are a ubiquitous group and are natural constituents of the intestinal flora of nearly all animals and humans and can reach high levels in a variety of farmhouse cheeses. The purpose of this study was to determine the origin of the different enterococcal strains present in cheeses at different stages of ripening by typing the enterococci isolated from the raw milk, the cheeses, the cheesemaking environment, and from the faecal matter of the ewes and humans associated with cheese production. The potential presence of vancomycin-resistant enterococci (VRE) at all stages of the process and in the cheeses was also considered. The study was carried out at two separate cheesemaking dairy plants, and samples of the ewes' faeces, the shepherds' and cheesemakers' stools, teat cups, vat, brine, holding tank milk, vat milk, and the cheeses after brining and after 1, 15, and 60 days of ripening were collected. Cheesemaking procedures at the two plants were similar, yet the enterococcal levels and species observed differed at all the sample collection points, though E. faecalis predominated in all the milk and cheese samples. The traceability study performed for the species E. faecalis present at all the sample collection points suggested that the cheesemaker and the cheesemaking equipment were the source of the enterococci in the cheeses, though other possible non-faecal sources remain to be determined. VanC1 and vanC2/C3 enterococcal strains were isolated from the ovine faeces, teat cup, brine, and vat samples at cheesemaking dairy plant A, while only two vanC2/C3 strains were isolated from ovine faeces samples at dairy plant B. No VRE strains were detected in any of the milk or cheese samples.

A multicentre report from the Mexican Retinoblastoma Group.

BACKGROUND: Retinoblastoma (RB) is a relatively uncommon tumour in childhood. The incidence of retinoblastoma in Mexico is probably higher than the incidence reported worldwide, however there is not enough information about the characteristics of this illness in Mexico. This report aims to present the results of a multicentre clinical survey of RB in Mexico. METHODS: A retrospective study was carried out on all RB cases treated in 16 institutions during the last six years. The variables analysed were age at diagnosis, sex, affected eyes, treatment modalities, and pathological staging. Overall survival was obtained. RESULTS: The authors analysed 500 cases; age range was 0-182 months. There were 364 unilateral cases (72.8%). Enucleation was performed in 84.9% of the patients. The St Jude's staging was: 7.4% stage I, 52.8% stage II, 18.0% stage III, 11.4% stage IV, 7.2% not evaluated, and 3.2% missing data. Chemotherapy was used in 74.4% of the patients. Disease free survival was 89% at 73 months follow up. CONCLUSIONS: The paper presents a great number of cases and pioneers multicentre studies in paediatric ophthalmology and oncology in this country. Given the great number of patients in advanced stages and the variability on treatment schemes, it is evident that it is mandatory to work in a cooperative group and develop a national early detection programme as well as a treatment protocol which include all specialists involved in the care of patients with RB.

Evaluation of the effect of rennet type on casein proteolysis in an ovine milk cheese by means of capillary electrophoresis.

Capillary electrophoresis was used to study the evolution of casein throughout the ripening process of Roncal Denomination of Origin ewe's milk cheese and to assess the type of rennet in its hydrolysis. Two manufactures were prepared, each with four vats; two of them had added lamb artisan rennet, batch A [clotting activity of 97.54 rennet units (RU) ml(-1)] and batch B [clotting activity of 16.26 RU ml(-1)]; one vat included calf industrial rennet, batch I (clotting activity of 45.70 RU ml(-1)); and the fourth vat had added mixed rennet, batch M, a 50:50 mixture of lamb (batch A) and calf (batch I) (clotting activity of 77.53 RU ml(-1)). The content of casein nitrogen in fractions alpha-casein1CE, alpha-casein2CE, beta-casein1CE and beta-casein2CE was quantified in cheese after 1, 15, 30, 60, 120 and 180 days of ripening. Beta-casein fractions undergo lesser degradation during the ripening time than alpha-casein proteins. The degradation of alpha-caseins is very much influenced by the clotting activity of the rennet used, so that the more active the clotting activity the greater the hydrolysis of those caseins. Nevertheless, it is at the level of beta-caseins that we observe the evidence of the influence of the type of rennet, thus noting a less intense proteolytic activity in the batch made with calf rennet, batch I.

Effect of the activity levels of the added proteolytic enzyme mixture on free amino acids in ripening Ossau-Iraty cheese.

A proteolytic enzymatic preparation (using one of three enzyme concentrations and, hence, one of three different enzymatic activity levels) was added (before clotting) to the milk used to manufacture Ossau-Iraty ewes'-milk cheese. The free amino acids were analysed by reversed-phase high-performance liquid chromatography and the sulphosalicylic acid-soluble N fraction was quantified by the trinitrobenzenesulphonic acid method for use as an index of proteolysis during ripening. Sensory analysis of the cheeses began after two months of ripening. Use of the enzymatic preparation increased the rate of release of amino acids in an amount proportional to the enzyme concentration employed. The effect of the preparation was more pronounced in the early months of ripening, with the differences in the free amino acid contents of the various batches decreasing as ripening progressed. Levels of certain free amino acids, such as taurine, tyrosine and valine, were virtually unaffected by the addition of the enzymatic preparation, whereas levels of such amino acids as serine, glycine, arginine and proline were reduced. Texture defects in the cheeses were observed, namely, reduced elasticity and creaminess and increased brittleness. Similarly, enzymatic treatment also gave rise to bitter flavours that were not characteristic of the normal taste and aftertaste of Ossau-Iraty cheese and these changes were proportional to the quantity of enzyme added.

Partial replacement of sodium chloride with potassium chloride in dry fermented sausages: Influence on carbohydrate fermentation and the nitrosation process.

Two types of dry fermented sausages were manufactured: type A with traditional formulation and type B with reduced sodium content. pH and a(w) values and the counts of aerobic mesophiles, Enterobacteriaceae and lactobacilli micro-organisms during the ripening of both fermented sausages were similar. Final lactic acid contents were also similar, but carbohydrate content was significantly lower in type B sausage. Content of acetic, propionic and butyric acids were significantly higher in type B, suggesting a higher heterofermentative activity. Also type B sausage showed lower nitrate level and higher chemical conversion percentage, suggesting a higher nitrosation intensity.

[Hepatosplenic sarcoidosis. Apropos of a case]. / Sarcoidosis hepatoesplénica. A propósito de una observación.

We present a case of hepatosplenic sarcoidosis without associated pulmonary affection. We have also revised the literature in this respect with special emphasis on the etiopathogenic aspects. The evolution and treatment followed during the period two liver biopsies were performed. The good response to treatment with steroids, clinically and histopathologically, are commented on.

Effect of lactobacillus adjunct cultures on the microbiological and physicochemical characteristics of Roncal-type ewes'-milk cheese.

The effect of two different experimental adjunct cultures composed of native facultatively heterofermentative lactobacilli (FHL) on the development of various groups of micro-organisms in Roncal-type ewes' milk cheese was studied. Four cheese batches were manufactured from raw milk (C), pasteurized milk (P), pasteurized milk and an adjunct culture of Lactobacillus paracasei (PP); and pasteurized milk and adjunct culture of Lactobacillus paracasei plus Lactobacillus plantarum (PPP). Retention of the two adjunct cultures in the cheeses was good, and population levels remained constant at around 10(7) cfu g(-1) of cheese throughout ripening. Levels of Enterobacteriaceae and enterococci fell off more abruptly in the batches made with the Lactobacillus adjunct cultures, suggesting competition between the added lactobacilli and those groups of micro-organisms. The inhibitory effect was greater for the adjunct culture composed of L. paracasei plus L. plantarum. Lactococcal levels were higher in the batches made with added FHL, which may be indicative of a synergistic effect between these two groups.