Exceptional continental record of biotic recovery after the Cretaceous-Paleogene mass extinction.

We report a time-calibrated stratigraphic section in Colorado that contains unusually complete fossils of mammals, reptiles, and plants and elucidates the drivers and tempo of biotic recovery during the poorly known first million years after the Cretaceous-Paleogene mass extinction (KPgE). Within ~100 thousand years (ka) post-KPgE, mammalian taxonomic richness doubled, and maximum mammalian body mass increased to near pre-KPgE levels. A threefold increase in maximum mammalian body mass and dietary niche specialization occurred at ~300 ka post-KPgE, concomitant with increased megafloral standing species richness. The appearance of additional large mammals occurred by ~700 ka post-KPgE, coincident with the first appearance of Leguminosae (the bean family). These concurrent plant and mammal originations and body-mass shifts coincide with warming intervals, suggesting that climate influenced post-KPgE biotic recovery.

Thyroid function in hidradenitis suppurativa: a population-based cross-sectional study from Denmark.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease. Numerous studies have associated HS with obesity, and recently with metabolic syndrome (MetS). Both obesity and MetS are linked with metabolic changes. Thyroid hormones play a central role in metabolism and exert pleiotropic effects on adipogenesis and the basal metabolism of lipids and glucose. We hypothesized that patients with HS have an altered or dysfunctional metabolism expressed as thyroid function. AIM: To investigate thyroid function in individuals with HS compared with healthy controls (HCs). METHODS: We conducted a retrospective comparative cross-sectional study using blood samples and questionnaire-based self-reported information to assess thyroid function. RESULTS: Our study comprised 430 patients in a population-based HS group, and 20 780 HCs. The age/sex-adjusted analysis showed a significantly lower level (P < 0.001) of thyroid-stimulating hormone (TSH) and a significantly higher level (P < 0.0001) of total triiodothyronine (tT3) for the HS compared with the HC group. The age/sex-adjusted analysis also showed a significant association between clinical hyperthyroidism and HS (an OR = 1.91, 95% CI 1.19-3.07; P = 0.02). When this analysis was adjusted further for the potential confounders of body mass index, smoking and oral contraception, the results remained significant. CONCLUSION: This study suggests that HS is associated with hyperthyroidism. Hyperthyroidism may indicate an altered or dysfunctional metabolism.

Hidradenitis suppurativa and electrocardiographic changes: a cross-sectional population study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease, recently associated with metabolic syndrome, subclinical atherosclerosis and increased risk of cardiovascular disease. OBJECTIVES: To investigate the hitherto unknown electrocardiographic (ECG) changes associated with HS, which have recently been associated with significant cardiovascular burden. METHODS: Data were obtained from the cross-sectional Danish General Population Study (GESUS). HS diagnosis was based on a validated self-reported questionnaire; 404 individuals met the HS diagnosis criteria and 19 001 controls without HS were identified. Severity of HS was staged according to a modified Hurley score. The ECG parameters of heart rate (HR), PR interval, QRS duration, JTc interval and QTc interval were obtained from 12-lead resting ECGs. We investigated the difference in means by unpaired t-test or anova. RESULTS: HR was significantly higher [mean difference 2·3 beats per min (bpm), 95% confidence interval (CI) 1·2-3·4; P < 0·01] when adjusting for age and sex, but when adjusting for multivariates, there was no significant difference (0·3 bpm, 95% CI -0·7 to 1·4; P = 0·52). Severe HS was significantly associated with increased HR across all models (2·9 bpm, 95% CI 0·7-5·1; P = 0·01). Mean QRS duration was significantly shorter in the group with mild HS but not in the groups with moderate and severe HS. CONCLUSIONS: Mean resting HR in patients with severe HS was significantly higher compared with controls. Given that resting HR is associated with increased risk of all-cause and cardiovascular mortality, and that patients with HS have increased risk of cardiovascular events, this finding is potentially important, easily testable and intervenable.

Moderate to severe hidradenitis suppurativa patients do not have an altered bacterial composition in peripheral blood compared to healthy controls.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels and scarring involving the intertriginous skin. Patients with HS often report an array of systemic symptoms such as fatigue and malaise. The aetiology of these symptoms remains unclear. Previously, various bacteria have been associated with mature HS lesions, and bacteraemia has been reported in patients with HS using traditional culturing methods. Thus, we hypothesized that a low-grade bacteraemia contributes to the symptomatology in patients with HS. OBJECTIVE: To explore the potential presence of bacteraemia in patients with HS and healthy controls. METHOD: A case-control study. Compositions of bacteria in the blood of 27 moderate to severe HS patients and 26 healthy controls were investigated using next-generation 16S ribosomal RNA gene sequencing (NGS) and routine anaerobic and aerobic blood culturing. None of the participants received any antibiotics (systemic or topical therapy) within 1 month prior to the study. HS patients with a recent flare were randomly selected by consecutive recruitment of eligible patients from the Department of Dermatology, Zealand University Hospital, Denmark. Healthy controls were recruited from the University of Copenhagen as well as from the healthcare staff. RESULTS: The different bacterial compositions were investigated using NGS and traditional anaerobic and aerobic blood culturing. Our NGS analysis provided a previously unreported characterization of the bacterial composition in peripheral blood from patients with HS and healthy controls. Overall, our data demonstrated that patients with HS do not have a different bacterial composition in their peripheral blood than healthy controls. CONCLUSION: The study suggests that the self-reported symptoms in HS such as malaise and fatigue may not be linked to bacteraemia.

Prodromal symptoms in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease, which presents as recurrent nodules and sinus tracts (tunnels) with subsequent scarring, predominantly involving the intertriginous regions. Although prodromal symptoms (i.e. various symptoms preceding the eruption of the HS lesions) are often mentioned, there have been no formal investigations into this aspect. Insight into prodromal symptoms may enable patients with HS or dermatologists in choosing a more targeted treatment at a much earlier stage, potentially increasing treatment efficacy and quality of life. AIM: To characterize the spectrum of prodromes in patients with HS. METHODS: An extensive questionnaire that explored the frequency, type and time of occurrence of the prodromal symptom(s) and the degree of certainty of the perceived association was administered to 72 patients. RESULTS: The majority of the 72 patients (83.3%; n = 60) confirmed that they experienced one or more symptom(s) prior to the development of inflamed nodules or abscesses. These included: fatigue (32%), malaise (defined as a fever-like sensation) (23%), headache (11%) and nausea (2%). Localized symptoms included skin erythema (75%), paraesthesia (63%) and itching (20%). the majority of the patients stated that the prodromes usually occurred > 24 h (45%) or 12-24 h (20%) before the eruption. CONCLUSION: Our data suggest that the majority of patients with HS experience prodromal symptoms, heralding a flare of their HS. The findings may give rise to important new treatment approaches for the management of HS.

Bacterial biofilm in chronic lesions of hidradenitis suppurativa.

BACKGROUND: Chronic nonhealing or recurrent inflammatory lesions, reminiscent of infection but recalcitrant to antibiotic therapy, generally characterize biofilm-driven diseases. Chronic lesions of hidradenitis suppurativa (HS) exhibit several characteristics, which are compatible with well-known biofilm infections. OBJECTIVES: To determine and quantify the potential presence of bacterial aggregates in chronic HS lesions. METHODS: In 42 consecutive patients with HS suffering from chronic lesions, biopsies were obtained from lesional as well as from perilesional skin. Samples were investigated using peptide nucleic acid-fluorescence in situ hybridization in combination with confocal laser scanning microscopy. In addition, corresponding histopathological analysis on haematoxylin and eosin slides was performed. RESULTS: Biofilms were seen in 67% of the samples of chronic lesions and in 75% of the perilesional samples. The mean diameter of aggregates in lesional skin was significantly greater than in perilesional skin (P = 0·01). Large biofilms (aggregates > 50 µm in diameter) were found in 42% of lesional samples and in only 5% of the perilesional samples (P = 0·009). The majority of the large biofilms were situated in sinus tracts (63%) or in the infundibulum (37%). The majority of the sinus tract samples (73%) contained active bacterial cells, which were associated with inflammation. CONCLUSIONS: This study suggests that biofilm formation is associated with inflammation of chronic HS lesions. The aggregates most likely occur as a secondary event, possibly due to predisposing local anatomical changes such as sinus tracts (tunnels), keratinous detritus and dilated hair follicles.

Is hidradenitis suppurativa associated with anaemia?: a population-based and hospital-based cross-sectional study from Denmark.

BACKGROUND: Chronic inflammatory diseases may be associated with anaemia of inflammation. Hidradenitis suppurativa is a chronic inflammatory dermatological disease associated with metabolic comorbidities, low quality of life and fatigue. Anaemia may cause fatigue, and it has been hypothesized that HS-related fatigue may be partly due to anaemia. OBJECTIVE: Our objective was to investigate a possible association between HS and anaemia. METHODS: We performed a hospital-based and population-based cross-sectional study investigating the red blood cell profile, i.e. haemoglobin. RESULTS: We identified a total of 32 hospital HS individuals, 430 population HS individuals and 20,780 population non-HS control individuals. The age-sex-smoking-adjusted analyses showed no differences in the haemoglobin level of the HS groups vs. the control group. Analyses of the anaemic subgroup of HS individuals revealed that 60% had normocytic anaemia and 40% microcytic anaemia, in concordance with anaemia of inflammation. CONCLUSION: In contrast to our hypothesis, this study showed that HS is not associated with anaemia. Thus, anaemia may not be the cause of the described fatigue in HS patients. Furthermore, the results indicate that if an HS patient does suffer from anaemia it is most likely to be normocytic or microcytic and thus compatible with anaemia seen in other chronic inflammatory disorders.

Body composition and basal metabolic rate in Hidradenitis Suppurativa: a Danish population-based and hospital-based cross-sectional study.

BACKGROUND: Several studies have suggested an association between Hidradenitis Suppurativa (HS) and obesity. Obesity is often expressed as Body Mass Index (BMI). However, BMI lacks information on body composition. General obesity is a predictor of health status and cardiovascular risk, but body composition (e.g. abdominal fat) may be more so. Basal metabolic rate (BMR) is an expression of resting metabolism and may serve as a complementary tool when assessing the possibly underlying metabolism behind a persons' body composition. OBJECTIVE: To investigate the body composition and basal metabolic rate in individuals with HS compared with healthy controls. METHODS: We performed a cross-sectional study on both a hospital-based and population-based HS group and compared with controls using Bioelectrical Impedance Analysis to assess body composition. RESULTS: We identified a hospital-based HS group of 32 hospital HS patients, a population-based HS group of 430 population HS patients, and 20 780 controls. Age- and sex-adjusted analyses showed a 10.12% (P < 0.0001) significantly higher fat percentage in the hospital-based HS group and 3.11% (P < 0.0001) significantly higher fat percentage for the population-based HS group compared to controls. Correspondingly, the HS groups had a lower muscle percentage (P < 0.0001) and lower bone mass percentage (P < 0.0001). Furthermore, visceral fat rating (P < 0.0001), Body Mass Index (P < 0.0001), waist circumference (P < 0.0001), and Waist/Hip Ratio (P < 0.0001) was significantly higher in HS patients compared with controls. Additionally, age and sex-adjusted analyses showed a higher predicted estimate of BMR for the HS groups compared with controls (154.56 kcal/day (95% CI 54.96-254.16) (P = 0.0031) for the hospital-based HS group, and 82.63 kcal/day (95%CI 59.70-105.56) (P < 0.0001) for the population-based HS group). CONCLUSION: Hidradenitis Suppurativa is associated with a high fat percentage, high visceral fat, and low muscle percentage adding to the morbidity of HS. The higher predicted estimate of basal metabolic rate (BMR) in HS patients may reflect a dysfunctional metabolism contributing to the high-fat-body composition.

The association of metabolic syndrome and psoriasis: a population- and hospital-based cross-sectional study.

BACKGROUND: Psoriasis (PS) has been suggested to be associated with the metabolic syndrome (MetS) in numerous studies with conflicting results. The vast majority of previous data were based on PS subjects from hospitals, and when based on data from the general population the PS subjects were often identified in insurance health databases. Furthermore, many studies used a single method approach, e.g. self-reported diagnosis. OBJECTIVE: We have therefore investigated a possible association between PS and MetS on PS subjects from the hospital as well as the general population using combined methods, i.e. self-reported diagnosis, physical examinations and blood samples. METHODS: A population- and hospital-based cross-sectional study of the possible association between PS and MetS. RESULTS: Thirty-six hospital PS subjects, 860 population PS subjects and 14,016 non-PS subjects were identified. The odds ratios (ORs) for hospital PS subjects and population PS subjects vs. population non-PS subjects, respectively, were 5.14 (2.47-10.69) and 1.29 (1.09-1.53) for MetS, 4.55 (1.91-10.85) and 1.16 (0.85-1.59) for diabetes, 1.92 (0.87-4.22) and 1.00 (0.86-1.17) for hypertension, 4.34 (1.86-10.10) and 1.15 (1.00-1.34) for hypertriglyceridaemia, 3.88 (1.96-7.69) and 1.19 (1.01-1.42) for hypoHDL, 5.77 (2.89-11.52) and 1.19 (1.00-1.41) for general obesity and 2.92 (1.45-5.88) and 1.34 (1.16-1.55) for abdominal obesity. Obesity acted as a possible confounder. A uniform pattern of higher ORs for hospital PS subjects when compared to population PS subjects was observed. The severity and duration of PS did not seem to affect the results. As this is a cross-sectional study we cannot demonstrate causality. CONCLUSION: The data suggested an association between PS and MetS as well as its individual parameters on a hospital-based level, with the exception of hypertension. On a population-based level the associations were only significant for MetS, hypoHDL and abdominal obesity.

The prevalence of inverse recurrent suppuration: a population-based study of possible hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving inverse recurrent suppuration (IRS). The epidemiology of the disease is not well described, with previous studies reporting prevalence estimates from 0·00033% to 4%. OBJECTIVE: To determine the prevalence of IRS in a large population-based survey. METHODS: Data were obtained from a general cross-sectional population study in Denmark. A validated self-administered questionnaire was used to identify IRS. Persons with the combination of outbreaks of 'boils' during the last 6 months in predefined areas and a minimum of two boils were identified. RESULTS: A total of 16 404 adults aged 30-89 years provided data and the overall prevalence of IRS was found to be 2·10% [95% confidence interval (CI) 1·88-2·32]; in men it was 1·58% (95% CI 1·29-1·86) and in women 2·56% (95% CI 2·21-2·86). No data for adults aged 20-29 years were included. The prevalence declined with age. The majority of cases (72·9%) had a body mass index of ≥ 25 kg m(-2) and 77·7% were current or ex-smokers. The mean number of inflamed lesions was 6·5 (range 2-67) during the last 6 months. The lesions affected mostly the genitalia (43·4%) and groin (39·8%) for women and 'other places' (not specified) (78·8%) for men. CONCLUSIONS: Data on IRS suggest that HS may be more prevalent than previously suggested, and the prevalence may be comparable to other major dermatoses, e.g. psoriasis. However, as no physician examination was done, the risk of recall and information bias is a major limitation.

Quantifying cardiovascular disease risk factors in patients with psoriasis: a meta-analysis.

BACKGROUND: In a previous meta-analysis on categorical data we found an association between psoriasis and cardiovascular disease and associated risk factors. OBJECTIVES: To quantify the level of cardiovascular disease risk factors in order to provide additional data for the clinical management of the increased risk. METHODS: This was a meta-analysis of observational studies with continuous outcome using random-effects statistics. A systematic search of studies published before 25 October 2012 was conducted using the databases Medline, EMBASE, International Pharmaceutical Abstracts, PASCAL and BIOSIS. RESULTS: We included 59 studies with up to 18 666 cases and 50 724 controls. Psoriasis cases had a higher total cholesterol [weighted mean difference 8·83 mg dL(-1) , 95% confidence interval (CI) 2·94-14·72, P = 0·003 (= 0·23 mmol L(-1) )], higher low-density lipoprotein cholesterol [9·90 mg dL(-1) , 95% CI 1·56-18·20, P = 0·020 (= 0·25 mmol L(-1) )], higher triglyceride [16·32 mg dL(-1) , 95% CI 12·02-20·63, P < 0·001 (= 0·18 mmol L(-1) )], a higher systolic blood pressure (4·77 mmHg, 95% CI 1·62-7·92, P = 0·003), a higher diastolic blood pressure (2·99 mmHg, 95% CI 0·60-5·38, P = 0·014), higher body mass idex (0·73 kg m(-2) , 95% CI 0·37-1·09, P < 0·001), higher waist circumference (3·61 cm, 95% CI 2·12-5·10, P < 0·001), higher fasting glucose [3·52 mg dL(-1) , 95% CI 0·64-6·41, P = 0·017 (= 0·20 mmol L(-1) )], higher nonfasting glucose [11·70 mg dL(-1) , 95% CI 11·24-12·15, P < 0·001 (= 0·65 mmol L(-1) )] and a higher HbA1c [1·09 mmol mol(-1) , 95% CI 0·87-1·31, P < 0·001 (= 2·2%)]. CONCLUSIONS: From a preventive medicine perspective, the weighted mean differences between cases and controls are significant, and therefore relevant to the clinical management of patients with psoriasis.

Factors related to pain during routine photodynamic therapy: a descriptive study of 301 patients.

BACKGROUND: Pain may be a limiting factor in the use of photodynamic therapy (PDT). The consequences of the pain i.e. the resources spent on pain-intervention during routine PDT therapy are poorly described. OBJECTIVES: To describe the consequences of pain during PDT by describing the use of pain-reducing interventions in routine use. We studied the frequency as well as level of pain-reducing intervention. METHODS: Descriptive data from PDT treated patients. The level of pain-reducing intervention was graded 0, no intervention; +, cold water spray and ++, pause or nerve block. RESULTS: Data from 983 PDT treatments on 579 lesions distributed on 301 patients: 56% did not require pain-reducing intervention, 35% required spraying of cold water, while 9% required pause or nerve block. Ordinate logistic regression revealed an association between lesion size and pain-reducing intervention: the larger the lesion, the more frequent the intervention. Lesion size did not, however, appear associated with the level of intervention. Intervention was most frequently required when treating the scalp/forehead and the extremities. The scalp/forehead also required the highest level of intervention. No significant association between pain-reducing intervention and diagnosis, pre-treatment, gender or age was found. CONCLUSIONS: Pain-reducing intervention was required in 44% of the PDT treatments. Intervention was particularly required when treating lesions in areas suited for PDT therapy for cosmetic reasons such as the scalp/forehead or extremities. Treatment of large areas more frequently calls for pain intervention than treatment of small areas.

Hidradenitis suppurativa and Crohn's disease: two cases that support an association.

An association between Crohn's disease and hidradenitis suppurativa has been suggested. The presence of Crohn's disease generally precedes the diagnosis of hidradenitis suppurativa. We present two new cases in which hidradenitis lesions developed before Crohn's disease, suggesting an overlap and supporting an association. Furthermore, in one of these cases, treatment with infliximab resulted in marked improvement in both the Crohn's disease and hidradenitis suppurativa.

Peripheral primitive neuroectodermal tumour of the hand in an adult.

We present a case of a 28 year-old woman who presented with a peripheral primitive neuroectodermal tumour of the right hand involving the fifth metacarpal and little finger. She underwent excision biopsy, then ray amputation of her right little finger. Initial radiological staging did not reveal metastasis but, after recurrence locally at two years and in spite of adjuvant chemotherapy and radiotherapy, the patient died of progressive metastatic disease 4 years later. The current concepts and difficulties in diagnosing these tumours are discussed.

Lost human capital from early-onset chronic depression.

OBJECTIVE: Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. METHOD: The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. RESULTS: Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. CONCLUSIONS: Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

Topically administered norfloxacin compared with topically administered gentamicin for the treatment of external ocular bacterial infections. The Worldwide Norfloxacin Ophthalmic Study Group.

In this double-masked study, we randomly assigned 488 patients with clinical signs of acute bacterial conjunctivitis or blepharitis, or both, to treatment with either norfloxacin ophthalmic solution 0.3% (245) or gentamicin ophthalmic solution 0.3% (243) for one week. Of the patients with positive cultures, 71% (85 of 120) of the norfloxacin-treated patients and 65% (86 of 133) of the gentamicin-treated patients were clinically cured. An additional 25% (30 of 120) of norfloxacin-treated patients and 32% (43 of 133) of gentamicin-treated patients were clinically improved. On the basis of posttreatment cultures, 89% of all cultured bacteria were eradicated (146 of 179 organisms) or suppressed (14 of 179 organisms) after treatment with norfloxacin. The condition of five norfloxacin-treated patients did not clinically improve, compared with the condition of eight gentamicin-treated patients. Both antibiotics had similar efficacy against gram-positive and against gram-negative organisms. One norfloxacin-treated patient and two gentamicin-treated patients withdrew from the study because of local intolerance. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the eyelids or conjunctiva, or both. In this study, norfloxacin was clinically and microbiologically similar in activity to gentamicin.