mRNA Levels of Aromatase, 5α-Reductase Isozymes, and Prostate Cancer-Related Genes in Plucked Hair from Young Men with Androgenic Alopecia.

Androgenic alopecia (AGA) is the most prevalent type of progressive hair loss and has psychological repercussions. Nevertheless, the effectiveness of current pharmacological treatments remains limited, in part because the molecular basis of the disease has not been fully elucidated. Our group previously highlighted the important roles of aromatase and 5α-reductase (5α-R) in alopecia in young women with female pattern hair loss. Additionally, an association has been proposed between AGA and prostate cancer (PCa), suggesting that genes implicated in PCa would also be involved in AGA. A low-invasive, sensitive, and precise method was used to determine mRNA levels of aromatase, 5α-R isozymes, and 84 PCa-related genes in samples of plucked hair from young men with AGA and controls. Samples were obtained with a trichogram from the vertex scalp, and mRNA levels were quantified using real-time RT-PCR. The men with AGA had significantly higher 5α-R2 mRNA levels in comparison to controls; interestingly, some of them also showed markedly elevated mRNA levels of 5α-R1 or 5α-R3 or of both, which may explain the varied response to 5α-R inhibitor treatments. The men with AGA also showed significant changes versus controls in 6 out of the 84 genes implicated in PCa. This study contributes greater knowledge of the molecular bases of AGA, facilitating early selection of the most appropriate pharmacological therapy and opening the way to novel treatments.

Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19.

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Corticosteroid Pulses for Hospitalized Patients with COVID-19: Effects on Mortality.

OBJECTIVES: To assess the influence of corticosteroid pulses on 60-day mortality in hospitalized patients with severe COVID-19. METHODS: We designed a multicenter retrospective cohort study in three teaching hospitals of Castilla y León, Spain (865,096 people). We selected patients with confirmed COVID-19 and lung involvement with a pO2/FiO2<300, excluding those exposed to immunosuppressors before or during hospitalization, patients terminally ill at admission, or those who died in the first 24 hours. We performed a propensity score matching (PSM) adjusting covariates that modify the probability of being treated. Then, we used a Cox regression model in the PSM group to consider factors affecting mortality. RESULTS: From 2933 patients, 257 fulfilled the inclusion and exclusion criteria. 124 patients were on corticosteroid pulses (250 mg of methylprednisolone for three days), and 133 were not. 30.3% (37/122) of patients died in the corticosteroid pulse group and 42.9% (57/133) in the nonexposed cohort. These differences (12.6%, 95% CI [8·54-16.65]) were statically significant (log-rank 4.72, p = 0, 03). We performed PSM using the exact method. Mortality differences remained in the PSM group (log-rank 5.31, p = 0.021) and were still significant after a Cox regression model (HR for corticosteroid pulses 0.561; p = 0.039). CONCLUSIONS: This study provides evidence about treatment with corticosteroid pulses in severe COVID-19 that might significantly reduce mortality. Strict inclusion and exclusion criteria with that selection process set a reliable frame to compare mortality in both the exposed and nonexposed groups.

Folliculitis decalvans: Effectiveness of therapies and prognostic factors in a multicenter series of 60 patients with long-term follow-up.

BACKGROUND: Folliculitis decalvans (FD) is a rare neutrophilic cicatricial alopecia that poses a therapeutic challenge. OBJECTIVES: To describe the therapeutic response in a large number of cases of FD with long-term follow-up and analyze potential prognostic factors associated with severity of form and with a better therapeutic response. METHODS: This multicenter prospective study included patients with FD who had a minimum of 5 years of follow-up. Severity was assessed by the maximum diameter of the cicatricial area. Therapeutic response was evaluated according to stabilization of the size of the cicatricial areas and the improvement in clinical symptoms. RESULTS: A total of 60 patients (37 men [61.7%] and 23 women [38.3%]) with a mean age of 40 years were included. Earlier age of onset (P = .01) was statistically associated with severity of form. Treatment with rifampicin and clindamycin, tetracyclines, and intralesional steroids was the most effective. No statistically significant prognostic factors predicting a better therapeutic response were found. LIMITATIONS: Because FD is a rare disease, the main limitation was the sample size. CONCLUSIONS: An earlier age of onset was associated with the severe form of the disease. The proposed specific therapeutic protocol can be a very useful tool in clinical dermatologic practice.

Frontal fibrosing alopecia: a multicenter review of 355 patients.

BACKGROUND: To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. OBJECTIVE: We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. METHODS: This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. RESULTS: In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). LIMITATIONS: The retrospective design is a limitation. CONCLUSIONS: Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment.

Evolution and Prognostic Significance of Patient-Reported Symptoms After Intervention in Severe Aortic Stenosis.

OBJECTIVE: To describe the evolution of symptoms in patients with symptomatic severe aortic stenosis (sSAS) undergoing valve replacement, the predictors of the persistence of these symptoms, and their prognostic significance. The evolution of symptoms after intervention in sSAS and their association with outcome are unknown. PATIENTS AND METHODS: Data from patients with sSAS who underwent intervention were collected. All-cause mortality and cardiovascular mortality were considered events. The evolution of symptoms and their association with events were studied. RESULTS: In this study, 451 consecutive patients with sSAS and no other valvular or coronary disease who were alive 30 days after intervention were included. Before valve replacement, 133 of the 451 patients (29.5%) had congestive heart failure requiring hospitalization. Of the remaining 318 patients, 287 (90.2%) had dyspnea on effort, 129 (40.6%) had angina, and 59 had syncope (18.6%). Symptoms disappeared after intervention in 192 of the 451 patients (42.6%) and remained in 259 (57.4%): 193 dyspnea, 9 angina, 17 syncope, and 60 admission for heart failure. Syncope on effort persisted in 4 of 33 patients (12.1%) and at rest in 11 of 20 (55.0%; P<.001). Age, body mass index, previous admission for heart failure, and chronic obstructive pulmonary disease were independently related to persistence of symptoms. Over a median follow-up of 56 months in our cohort of 451 patients, 129 deaths were registered (28.6%), 40 of which were cardiovascular (8.9%). Age, chronic obstructive pulmonary disease, chronic kidney disease, atrial fibrillation, heart failure, and persistence of symptoms were independently associated with all-cause mortality. CONCLUSION: Symptoms attributed to SAS remain after intervention in a high proportion of patients, particularly dyspnea on effort and syncope at rest. The persistence of symptoms after intervention identifies patients with poor outcome.

3D Virtual modelling, 3D printing and extended reality for planning of implant procedure of short-term and long-term mechanical circulatory support devices and heart transplantation.

Introduction: The use of three-dimensional (3D) reconstruction and printing technology, together with extended reality applied to advanced heart failure adult patients with complex anatomy, is rapidly spreading in clinical practice. We report practical experience with application to acute and chronic heart failure: planning and performing mechanical circulatory device insertion or heart transplantation. Methods: From November 2019 until February 2022, 53 3D virtual biomodels were produced for intervention planning (using Virtual/Augmented Reality and/or 3D printing), following a specific segmentation and preprocessing workflow for biomodelling, in patients with advanced heart failure due to structural heart disease or cardiomyopathies. Four of those patients were complex cases requiring mechanical circulatory support implant procedures in our center. Results: One short-term and three long-term ventricular assist device system were successfully clinically implanted after application of this technique. In other two cases with extremely high procedural risk, visualized after application of this multimodality imaging, heart transplantation was elected. Conclusion: 3D printing based planning and virtual procedure simulation, are of great importance to select appropriate candidates for mechanical circulatory support in case of complex patient anatomy and may help to diminish periprocedural complications. Extended reality represents a perspective tool in planification of complex surgical procedures or ventricular assist device insertion in this setting.

Recurrence of syncope after valve replacement in severe aortic stenosis.

OBJECTIVE: The recurrence of syncope after valve intervention in severe aortic stenosis (SAS) and its impact on outcome are unknown. We hypothesised that syncope on exertion will disappear after intervention, whereas syncope at rest might recur. Our aim has been to describe the recurrence of syncope in patients with SAS undergoing valve replacement and its impact on mortality. METHODS: Double-centre observational registry of 320 consecutive patients with symptomatic SAS without other valve disease and/or coronary artery disease who underwent valve intervention and were discharged alive. All-cause mortality and cardiovascular mortality were considered events. RESULTS: 53 patients (median age 81 years, 28 men) had syncope (29 on exertion, 21 at rest, 3 unknown). Clinical and echocardiographic variables were similar in patients with and without syncope (median vmax 4.44 m/s, mean gradient 47 mm Hg, valve area 0.7 cm2, left ventricular ejection fraction 62%). After a median follow-up of 69 months (IQR: 55-88), syncope on exertion did not recur in any patient. In contrast, 8 of the 21 patients with syncope at rest had postintervention syncope at rest (38%; p<0.001): 3 needed a pacemaker, 3 were neuromediated or hypotensive and 2 arrhythmic. Only recurrence of syncope was associated with cardiovascular mortality (HR 5.74; 95% CI 2.17 to 15.17; p<0.001). CONCLUSIONS: Syncope on exertion in patients with SAS did not recur after aortic valve intervention. Syncope at rest recurs in a high proportion of patients and identifies a population with increased mortality. According to our results, syncope at rest should be thoroughly evaluated before proceeding to aortic valve intervention.

Exercise Intolerance in Post-Acute Sequelae of COVID-19 and the Value of Cardiopulmonary Exercise Testing- a Mini-Review.

Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with systemic organ damage in the most severe forms. Long-term complications of SARS-CoV-2 appear to be restricted to severe presentations of COVID-19, but many patients with persistent symptoms have never been hospitalized. Post-acute sequelae of COVID-19 (PASC) represents a heterogeneous group of symptoms characterized by cardiovascular, general, respiratory, and neuropsychiatric sequelae. The pace of evidence acquisition with PASC has been rapid, but the mechanisms behind it are complex and not yet fully understood. In particular, exercise intolerance shares some features with other classic respiratory and cardiac disorders. However, cardiopulmonary exercise testing (CPET) provides a comprehensive assessment and can unmask the pathophysiological mechanism behind exercise intolerance in gray-zone PASC. This mini-review explores the utility of CPET and aims to provide a comprehensive assessment of PASC by summarizing the current evidence.

Commissural Versus Coronary Optimized Alignment During Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aims of this study were to determine the rate of noncentered coronary ostia and their risk for coronary overlap (CO) and to develop an improved orientation strategy for transcatheter aortic valve replacement (TAVR) devices taking into account anatomical cues to identify patients at risk for CO regardless of commissural alignment and compute an alternative, CO-free TAVR rotation angle for those patients. BACKGROUND: Commissural alignment during TAVR reduces CO risk. However, eccentricity of coronary ostia from the center of the sinus of Valsalva may result in CO even after perfect alignment of TAVR commissures. METHODS: Baseline computed tomography from TAVR candidates helped identify distance from commissures to the right coronary artery (RCA) and the left coronary artery (LCA). Then, for each case, a virtual valve was simulated with ideal commissural or coronary alignment, and the degree of CO was determined. On the basis of the potential BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) efficacy, 3 groups were defined: no risk for CO (>35° from neocommissure to coronary ostia), moderate risk (20°-35°), and severe risk (≤20°). RESULTS: Computed tomographic studies from 107 patients were included. After excluding 7 patients (poor quality or bicuspid valve), 100 patients were analyzed. The RCA showed greater eccentricity compared with the LCA (18.5° [IQR: 3.3°-12.8°] vs 6.5° [IQR: 3.3°-12.8°]; P < 0.001). The mean intercoronary angle was 140.0° ± 18.7° (95% CI: 136.3°-143.7°). Thirty-two patients had moderate to severe risk for CO (≤35°) despite ideal commissural alignment. Greater coronary eccentricity (cutoff for RCA, 24.5°; cutoff for LCA, 19°) and intercoronary angle >147.5° or <103° were associated with greater risk for moderate to severe CO despite commissural alignment (area under the curve: 0.97; 95% CI: 0.91-0.99). If optimal coronary alignment was simulated, this prevented severe CO in all cases and reduced moderate CO from 27% to 5% (P < 0.001). CONCLUSIONS: One third of patients would have CO during TAVR-in-TAVR despite commissural alignment; a 6-fold decrease in this risk was achieved with optimized coronary alignment. Coronary eccentricity and intercoronary angle were the main predictors.

Cardio-Pulmonary Dysfunction Evaluation in Patients with Persistent Post-COVID-19 Headache.

Background (1): Headache is a prevalent symptom experienced during ongoing SARS-CoV-2 infection, but also weeks after recovery. Whether cardio-pulmonary dysfunction contributes causally to headache persistence is unknown. Methods (2): We conducted a case-control analysis nested in a prospective cohort study. Individuals were recruited from August 2020 to December 2020. Patients were grouped according to the presence or absence of long-COVID headache for three months after COVID-19 resolution. We compared demographic data, clinical variables, cardio-pulmonary laboratory biomarkers, quality of life, and cardio-pulmonary function between groups. Results (3): A cohort of 70 COVID-19 patients was evaluated. Patients with headaches (n = 10; 14.3%) were more frequently female (100% vs. 58.4%; p = 0.011) and younger (46.9 ± 8.45 vs. 56.13 ± 12 years; p = 0.023). No between-group differences in laboratory analysis, resting echocardiography, cardio-pulmonary exercise test, or pulmonary function tests were observed. Conclusion (4): In this exploratory study, no significant differences in cardio-pulmonary dysfunction were observed between patients with and without long-COVID headache during mid-term follow-up.

Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. METHODS: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. RESULTS: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO2 consumption (77.8 (64-92.5) vs. 99 (88-105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467-600) vs. 611 (550-650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VCO2 slope 32 (28.1-37.4) vs. 29.4 (26.9-31.4); p = 0.022) and high PETCO2 (34.5 (32-39) vs. 38 (36-40); p = 0.025). INTERPRETATION: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.

Onychomycosis by Chaetomium spp.

Onychomycosis is one of the most common infections of the nail. It can be caused by dermatophytes, Candida species and other fungi. Although moulds can cause onychomycosis, they account for a minority of cases, mainly great toenail onychomycosis. We describe a case of an 11-year-old girl who developed an onychomycosis by Chaetomium species in second and third toenails.

Programmatic human papillomavirus testing in cervical cancer prevention in the Jujuy Demonstration Project in Argentina: a population-based, before-and-after retrospective cohort study.

BACKGROUND: Human papillomavirus (HPV) testing for cervical cancer prevention was introduced in Argentina through the Jujuy Demonstration Project (2011-14). The programme tested women aged 30 years and older attending the public health system with clinician-collected HPV tests. HPV self-collection was introduced as a programmatic strategy in 2014. We aimed to evaluate the effectiveness of programmatic HPV testing to detect cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) in comparison with cytology-based screening. METHODS: We did a population-based, before-and-after retrospective cohort study using data from the National Cervical Cancer Prevention Program for the Jujuy province in northwest Argentina. We obtained data for the cytology-based screening period from Jan 1, 2010, until Dec 31, 2011, and for the HPV-based screening period from Jan 1, 2012, until Dec 31, 2014. The primary outcome was detection of histologically diagnosed CIN2+ among women aged 30 years and older. To assess the outcomes in all individuals included in the study, we used multivariable logistic regression and propensity score matching. The reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework was used for the before-and-after analysis of programmatic dimensions. FINDINGS: Of the 29 631 women who underwent cytology-based screening in 2010-11, CIN2+ was detected in 236 (0·8%) individuals. Of the 49 565 women HPV tested in 2012-14 (clinician-collected tests, n=44 700; self-collection tests, n=4865), 693 (1·4%; 658 clinician-collected tests; 35 self-collection tests) were found to have CIN2+ after the first round of screening. Compared with cytology-based screening, the odds ratio of being diagnosed with a CIN2+ lesion was 2·34 (95% CI 2·01-2·73; p<0·0010) with clinician-collected tests, and 1·08 (0·74-1·52; p=0·68) when screened with self-collection tests, after controlling for age and health insurance status. Screening coverage was similar in both periods (52·7% vs 53·2%); improvements of programmatic indicators were observed in the HPV testing period in relation to laboratory centralisation, lower overscreening (6·6% vs 0·0%), higher adherance to age recommendations (79·3% vs 98·8%), and a decrease of inadequate samples (3·6% vs 0·2%). INTERPRETATION: HPV testing in middle-income settings increases detection of CIN2+ lesions and allows for improvement of programmatic indicators. Evidence suggests that the introduction of HPV testing will accelerate the reduction of cervical cancer burden. FUNDING: Argentinian National Cancer Institute and National Council of Scientific and Technologic Research.

Amputation neuromas after neck surgery.

Traumatic or amputation neuromas are benign tumours formed by a proliferation of Schwann cells, axons and connective tissue elements. They are secondary to the partial or total section of a nerve pathway due to an accidental or surgical trauma. They can form at any site and affect any type of nerve. The presence of amputation neuromas is very frequent in major surgery but rare in simple excisions of skin tumours. We report two cases with neuroma localized in the neck, one after lymph node dissection for melanoma metastasis and the other after excision of a cutaneous melanoma with 3-cm margin on lateral neck. In both cases, the presence of the neuroma mandated a surgical excision to rule out a possible recurrence of melanoma.