Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron.

The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in November 2021 in South Africa and Botswana, as well as in a sample from a traveller from South Africa in Hong Kong1,2. Since then, Omicron has been detected globally. This variant appears to be at least as infectious as Delta (B.1.617.2), has already caused superspreader events3, and has outcompeted Delta within weeks in several countries and metropolitan areas. Omicron hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness2,4-6. Here we investigated the virus-neutralizing and spike protein-binding activity of sera from convalescent, double mRNA-vaccinated, mRNA-boosted, convalescent double-vaccinated and convalescent boosted individuals against wild-type, Beta (B.1.351) and Omicron SARS-CoV-2 isolates and spike proteins. Neutralizing activity of sera from convalescent and double-vaccinated participants was undetectable or very low against Omicron compared with the wild-type virus, whereas neutralizing activity of sera from individuals who had been exposed to spike three or four times through infection and vaccination was maintained, although at significantly reduced levels. Binding to the receptor-binding and N-terminal domains of the Omicron spike protein was reduced compared with binding to the wild type in convalescent unvaccinated individuals, but was mostly retained in vaccinated individuals.

Issues around food in mixed families of adolescent girls with bulimia nervosa: A qualitative study with photo-elicitation.

OBJECTIVES: Bulimia nervosa (BN) is a common psychiatric disorder among adolescent girls with potentially significant complications. Family relationships play a major role in the development and progression of this disorder. Studies in migrant populations suffering from eating disorders show contrasting results depending on the generation of migrants: first generation migrants have fewer eating disorders than the native population, while the prevalence of this disorder is more important than the latter among second and third generation migrants. In our clinical experience, we have frequently encountered so-called "mixed" families, which are families composed of one migrant parent and one non-migrant parent. Research focusing on this kind of family is scarce which is why we chose to explore their dynamic. METHODS: This study explored the issues around food and family relationships of adolescent girls suffering from BN, a topic that, to date, has not yet been studied. Ten interviews were conducted with five adolescent girls with BN between the ages of 16 and 20 and their parents, using photo-elicitation to enrich the collected data. RESULTS: The results were organized around two axes: (1) identity issues around food, that is the assimilation process described by both parents and adolescents concerning family meals and food habits, and how the adolescents struggle to manage this interbreeding; and (2) transmission issues with the consequences the migrant parent has to deal with to transmit his/her cultural identity with food while being far away from the homeland, and the difficulties between this parent and his/her child to share this heritage. Both issues, identity and transmission, appear to be central among these families. CONCLUSIONS: Our results suggest a difficulty in mentalizing identity issues in adolescent girls; the function of appeasement around non-mentalized tensions was highlighted. In our opinion, in this particular context, BN acts as a means of expressing the difficulty of their mixed culture. This enables it to draw some clinical implications, especially using mentalization-based therapy which has already shown efficacy in adolescents with borderline personality disorder and ED.

Intraoperative motive for incomplete resection in primary retroperitoneal sarcoma.

INTRODUCTION: Surgical resection is the current standard of care for retroperitoneal sarcoma (RPS). Recent data suggests that up to 5% of patient have incomplete (R2) resection. The exact reason why patients scheduled for surgery with a curative intent to treat ended up with an R2 resection is largely unknown. AIM OF THE STUDY: To identify intraoperative findings responsible for incomplete (R2) resection in primary RPS. METHODS: All records of consecutive patients scheduled for a non-metastatic primary RPS surgery between 1995 and 2020 in a tertiary care sarcoma centre were retrospective analyzed. RESULTS: Among the 347 patients scheduled for surgery, 13 (3.7%) had an incomplete (R2) resection. The reasons for incomplete surgery were intraoperative finding of vascular involvement of great vessels in 5 patients, previously undetected peritoneal metastases in 5 patients, invasion of contralateral kidney/ureter in 2 patients and the need to preserve both kidneys in 1 patient because of his past medical history. Among these patients, 3 had a laparotomy without resection and 10 had a partial resection (i.e. debulking surgery). Severe postoperative complications occurred in 5 patients. The median length of stay in hospital was 19days. After a median follow-up of 12months, the median survival of patients after incomplete resection was 18months. The 1-y, 5-y and 8-y overall survival (OS) for these patients were 46%, 14%, and 7%, respectively. CONCLUSION: Incomplete (R2) resection for a primary RPS surgery is rare in specialized sarcoma center. The next steps should be to identify the preoperative criteria that lead to this accurate selection and to define the best practice in front of a peroperative discovery of an unresectable RPS. LEVEL OF EVIDENCE: III.

Development and validation of a patient-reported outcome in systemic sclerosis: the Hand scleroDerma lived Experience (HAnDE) scale.

BACKGROUND: Hand involvement in systemic sclerosis (SSc) is at the core of the disease, with a substantial impact on both functional aspects and quality of life. There is no patient-reported outcome (PRO) scale globally assessing hand involvement in SSc. OBJECTIVES: To develop and validate a PRO scale, the Hand scleroDerma lived Experience (HAnDE) scale, to assess the lived experience of hand involvement in patients with SSc. METHODS: This was an exploratory sequential mixed-methods study with two phases: (i) PRO development through an inductive process to analyse the structure of lived experience, involving 21 patients with SSc; and (ii) PRO validation by assessing the psychometric properties of the scale among 105 patients with SSc. RESULTS: Phase 1 enabled us to generate the 18-item provisional scale. From Phase 2, the mean (SD) total score of the scale was 29·16 (16·15). The item reduction process retained 16 items with five levels of answers (range 0-64). Internal consistency of the 16-item version was excellent (Cronbach's alpha = 0·946). Construct validity was very good, principal component analysis pointing towards a unidimensional instrument, with one factor explaining 56% of the variance, and concurrent validity being confirmed: Cochin Hand Function Scale r = 0·66; Health Assessment Questionnaire - Disability index r = 0·58; Hospital Anxiety and Depression Scale, anxiety r = 0·51, depression r = 0·4; Mouth Handicap in Systemic Sclerosis scale r = 0·61; 36-Item Short Form Health Survey, physical component r = -0·48, mental component r = -0·46; and Kapandji score r = -0·46. The correlations were statistically significant (P < 0·05). CONCLUSIONS: We propose, for future trials and clinical practice in SSc, a new PRO, the HAnDE scale, that assesses all the dimensions - functional, aesthetic, relational, existential and emotional - of the lived experience of hand involvement in SSc.

First use of the Adolescent Depression Rating Scale (ADRS) in the management of young people with severe acne treated with isotretinoin: a pilot study of an active monitoring of depressive disorders by dermatologists.

BACKGROUND: During isotretinoin treatment, special attention is required to detect any symptom or change in the mental health of patients. The monitoring is complex for adolescents because of confounding factors such as mood changes associated with adolescence and puberty and the higher psychosocial impairment due to the acne itself. AIM: To determine the utility of the Adolescent Depression Rating Scale (ADRS) for monitoring symptoms in adolescents before and during isotretinoin treatment in dermatology real-life practice. METHODS: This was a national, multicentre prospective study that enrolled a random sample of dermatologists treating adolescents. An algorithm including ADRS score and its changes between consecutive visits was used. At each visit, dermatologists rated their satisfaction with ADRS and its ease of use, while patients rated the acceptability of the ADRS. RESULTS: In total, 70 dermatologists used the algorithm for 1227 visits of 283 adolescents receiving isotretinoin. Of these 70 dermatologists, 80.8% were satisfied/very satisfied with the ADRS, 82.7% considered the use of the ADRS in clinical practice to be easy/very easy and 75% considered that the ADRS enabled them to discuss more easily the risk of depression with their patients. For the patients, acceptability of the ADRS was considered good by 93.8%. CONCLUSIONS: The implementation of the ADRS could be valuable in dermatology practice, optimizing the monitoring of patients and the good use of isotretinoin.

Reduced disease severity following therapeutic treatment with angiotensin 1-7 in a mouse model of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by autoimmune and neurodegenerative pathologies for which there is no cure and no defined etiology. Although several, modestly effective, disease modifying drugs are available to treat MS, there are presently no treatments that offer neuroprotection and prevent clinical progression. Therapies are needed that control immune homeostasis, prevent disease progression, and stimulate regeneration in the CNS. Components of the renin-angiotensin-system (RAS) have recently been identified as chemical mediators in the CNS and in neurological disease. Here we show the beneficial effect of therapeutic treatment with the Mas receptor agonist and metabolite of the protective arm of RAS, angiotensin 1-7 (A(1-7)), in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Therapeutic treatment with A(1-7) caused a dose-dependent reduction both in clinical disease severity and progression, and was dependent on Mas receptor activation. Further analysis of the most optimal dose of A(1-7) treatment revealed that the reductions in clinical disease course were associated with decreased immune infiltration and demyelination, axonal loss and oxidative stress in the spinal cord. In addition A(1-7) treatment was also associated with increases in circulating alternatively activated monocytes/macrophages.

Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

This study compares the frequency and severity of influenza A/H1N1pdm09 (A/H1), influenza A/H3N2 (A/H3) and other respiratory virus infections in hospitalised patients. Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumovirus, respiratory syncytial virus and parainfluenza. Of these, 1753 (10.1%) had test results. Multivariable regression analyses were conducted to compare the viruses for clinical outcomes including ICU admission, ventilation, pneumonia, length of stay and death. Patients with A/H1 were more likely to experience severe outcomes such as ICU admission (OR 2.5, 95% CI 1.2-5.5, P = 0.016), pneumonia (OR 3.0, 95% CI 1.6-5.7, P < 0.001) and lower risk of discharge from hospital (indicating longer lengths of hospitalisation; HR 0.64 95% CI 0.47-0.88, P = 0.005), than patients with A/H3. Patients with a non-influenza respiratory virus were less likely to experience severe clinical outcomes than patients with A/H1, however, had similar likelihood when compared to patients with A/H3. Patients hospitalised with A/H1 had higher odds of severe outcomes than patients with A/H3 or other respiratory viruses. Knowledge of circulating influenza strains is important for healthcare preparedness.

Time to surgery after hip fracture across Canada by timing of admission.

The extent of Canadian provincial variation in hip fracture surgical timing is unclear. Provinces performed a similar proportion of surgeries within three inpatient days after adjustment. Time to surgery varied by timing of admission across provinces. This may reflect different approaches to providing access to hip fracture surgery. INTRODUCTION: The aim of this study was to compare whether time to surgery after hip fracture varies across Canadian provinces for surgically fit patients and their subgroups defined by timing of admission. METHODS: We retrieved hospitalization records for 140,235 patients 65 years and older, treated surgically for hip fracture between 2004 and 2012 in Canada (excluding Quebec). We studied the proportion of surgeries on admission day and within 3 inpatient days, and times required for 33%, 66%, and 90% of surgeries across provinces and by subgroups defined by timing of admission. Differences were adjusted for patient, injury, and care characteristics. RESULTS: Overall, provinces performed similar proportions of surgeries within the recommended three inpatient days, with all provinces requiring one additional day to perform the recommended 90% of surgeries. Prince Edward Island performed 7.0% more surgeries on admission day than Ontario irrespective of timing of admission (difference = 7.0; 95% CI 4.0, 9.9). The proportion of surgeries on admission day was 6.3% lower in Manitoba (difference = - 6.3; 95% CI - 12.1, - 0.6), and 7.7% lower in Saskatchewan (difference = - 7.7; 95% CI - 12.7, - 2.8) compared to Ontario. These differences persisted for late weekday and weekend admissions. The time required for 33%, 66%, and 90% of surgeries ranged from 1 to 2, 2-3, and 3-4 days, respectively, across provinces by timing of admission. CONCLUSIONS: Provinces performed similarly with respect to recommended time for hip fracture surgery. The proportion of surgeries on admission day, and time required to complete 33% and 66% of surgeries, varied across provinces and by timing of admission. This may reflect different provincial approaches to providing access to hip fracture surgery.

Risk of major congenital malformations following first-trimester exposure to vaginal azoles used for treating vulvovaginal candidiasis: a population-based retrospective cohort study.

OBJECTIVE: To evaluate the risk for major malformations following first-trimester exposure to vaginal azoles. DESIGN: A population-based retrospective cohort study of women exposed to vaginal azoles from the first day of the last menstrual period until the 90th gestational day. SETTING: A combination of four computerised databases: medications, birth, infant hospitalizations, and pregnancy terminations. POPULATION: All women who gave birth or underwent a pregnancy termination at Soroka Medical Center, Beer-Sheva, Israel, between 1999 and 2009. METHODS: Crude and adjusted relative risks for major congenital malformations and for specific malformations according to organ systems were calculated using a multivariate negative binomial regression. Potential confounders were assessed and controlled for included parity, maternal age, ethnicity, maternal diabetes, smoking, and year of birth or pregnancy termination. Additional analysis using propensity score matching was performed for selected malformations. MAIN OUTCOME MEASURES: Major malformations as well as specific malformations according to organ systems. RESULTS: Of 101 615 pregnancies, 1993 (1.96%) were exposed to clotrimazole vaginal tablets and 313 (0.31%) to miconazole vaginal tablets during the first trimester of pregnancy. No association was found between first-trimester exposure to clotrimazole and major or specific malformations. An association was found between miconazole exposure and musculoskeletal malformation in general and other congenital musculoskeletal anomalies in particular. However, no association was detected when propensity score matching was used. CONCLUSIONS: Intrauterine exposure to vaginal azoles during the first trimester of pregnancy was not associated with either major or specific malformations according to organ systems. TWEETABLE ABSTRACT: First-trimester exposure to vaginal azoles is not associated with either major or specific malformations.

Depletion of NADP(H) due to CD38 activation triggers endothelial dysfunction in the postischemic heart.

In the postischemic heart, coronary vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function. Although the eNOS cofactor tetrahydrobiopterin (BH4) is depleted, its repletion only partially restores eNOS-mediated coronary vasodilation, indicating that other critical factors trigger endothelial dysfunction. Therefore, studies were performed to characterize the unidentified factor(s) that trigger endothelial dysfunction in the postischemic heart. We observed that depletion of the eNOS substrate NADPH occurs in the postischemic heart with near total depletion from the endothelium, triggering impaired eNOS function and limiting BH4 rescue through NADPH-dependent salvage pathways. In isolated rat hearts subjected to 30 min of ischemia and reperfusion (I/R), depletion of the NADP(H) pool occurred and was most marked in the endothelium, with >85% depletion. Repletion of NADPH after I/R increased NOS-dependent coronary flow well above that with BH4 alone. With combined NADPH and BH4 repletion, full restoration of NOS-dependent coronary flow occurred. Profound endothelial NADPH depletion was identified to be due to marked activation of the NAD(P)ase-activity of CD38 and could be prevented by inhibition or specific knockdown of this protein. Depletion of the NADPH precursor, NADP(+), coincided with formation of 2'-phospho-ADP ribose, a CD38-derived signaling molecule. Inhibition of CD38 prevented NADP(H) depletion and preserved endothelium-dependent relaxation and NO generation with increased recovery of contractile function and decreased infarction in the postischemic heart. Thus, CD38 activation is an important cause of postischemic endothelial dysfunction and presents a novel therapeutic target for prevention of this dysfunction in unstable coronary syndromes.

The fetal safety of clomiphene citrate: a population-based retrospective cohort study.

OBJECTIVE: To evaluate whether exposure to clomiphene citrate (CC) for ovulation induction is associated with major malformations overall or with specific fetal anomalies. DESIGN: We conducted a population-based retrospective cohort study. Exposure was defined as CC dispension from 2 months before conception through the first month of pregnancy. SETTINGS: Four databases were combined: medication, birth, hospitalization, and terminations of pregnancy. POPULATION: The study included all women in southern Israel who gave birth or underwent termination of pregnancy at Soroka Medical Center, from 1998 to 2009. METHODS: The rates of major malformations overall and six different subcategories of anomalies were evaluated. The crude odds ratio (OR) was calculated with a 95% confidence interval (95% CI). Subsequently the adjusted odds ratio (aOR) was calculated using multiple logistic regression models controlling for maternal age, pre-pregnancy diabetes, parity, ethnicity, the calendar year in which the birth/termination of pregnancy took place, smoking, and the use of gonadotropins and progesterone. MAIN OUTCOME MEASURES: Major malformations overall and specific fetal malformations by organ systems. RESULTS: Of 114 961 pregnant women, 1872 were exposed to CC. No association was detected between exposure to CC and rates of major malformations overall (aOR 1.08, 95% CI 0.88-1.32) or rates of subcategories of malformations. Exposure was not associated with anencephaly (aOR 2.27, 95% CI 0.44-11.71) or oesophageal atresia (aOR 3.681, 95% CI, 0.65-20.76). CONCLUSIONS: In this large population-based retrospective cohort study, exposure to CC was not associated with an increased risk of either rates of major malformations overall or rates of specific malformations. TWEETABLE ABSTRACT: An observational study: no increased risk for fetal malformations following exposure to clomiphene citrate.

[Chromomycosis acquired in a non-tropical area: A case report]. / Une chromomycose contractée en zone non tropicale.

BACKGROUND: Chromomycosis, or chromoblastomycosis, is caused by cutaneous inoculation of dematiaceous fungi of telluric or plant origin. It is generally seen in tropical or subtropical zones. Treatment of the condition is known to be complex. Herein we report a case of chromomycosis contracted in a temperate region of Eastern Europe/Central Asia that was effectively treated with oral itraconazole and terbinafine in combination with cryotherapy. PATIENTS AND METHODS: A 44-year-old immunocompetent male subject consulted for a lesion on the buttocks that he had sustained 16 years earlier, and which, although never previously treated, had only become troublesome within the last few months. The examination revealed a large erythemato-squamous plaque containing a heterogeneous infiltrate. The diagnosis was based upon biopsy, with histological examination revealing sooty mould ; culture of a second sample showed the causative agent to be Fonsecaea pedrosoi. After 30 months of treatment combining oral terbinafine at a very high dose (1000mg/day), topical terbinafine and adjuvant cryotherapy, considerable, though incomplete, improvement was obtained. Finally, combined use of terbinafine (500mg/day) and itraconazole (200mg/day) led to clinical and histological cure. DISCUSSION: The possibility of acquiring chromomycosis other than in a tropical zone is slight but has nevertheless been described, particularly in Eastern Europe. In our patient, the exact source of contamination is unknown, although it may have been acquired through frequent horse-riding or use of saunas. This case confirms the efficacy of combined itraconazole and terbinafine against this condition, which is usually difficult to treat.

Mechanisms of extracellular S0 globule production and degradation in Chlorobaculumtepidum via dynamic cell-globule interactions.

The Chlorobiales are anoxygenic phototrophs that produce solid, extracellular elemental sulfur globules as an intermediate step in the oxidation of sulfide to sulfate. These organisms must export sulfur while preventing cell encrustation during S0 globule formation; during globule degradation they must find and mobilize the sulfur for intracellular oxidation to sulfate. To understand how the Chlorobiales address these challenges, we characterized the spatial relationships and physical dynamics of Chlorobaculum tepidum cells and S0 globules by light and electron microscopy. Cba. tepidum commonly formed globules at a distance from cells. Soluble polysulfides detected during globule production may allow for remote nucleation of globules. Polysulfides were also detected during globule degradation, probably produced as an intermediate of sulfur oxidation by attached cells. Polysulfides could feed unattached cells, which made up over 80% of the population and had comparable growth rates to attached cells. Given that S0 is formed remotely from cells, there is a question as to how cells are able to move toward S0 in order to attach. Time-lapse microscopy shows that Cba. tepidum is in fact capable of twitching motility, a finding supported by the presence of genes encoding type IV pili. Our results show how Cba. tepidum is able to avoid mineral encrustation and benefit from globule degradation even when not attached. In the environment, Cba. tepidum may also benefit from soluble sulfur species produced by other sulfur-oxidizing or sulfur-reducing bacteria as these organisms interact with its biogenic S0 globules.

Optical Emission Spectroscopy Study of Competing Phases of Electrons in the Second Landau Level.

Quantum phases of electrons in the filling factor range 2≤ν≤3 are probed by the weak optical emission from the partially populated second Landau level and spin wave measurements. Observations of optical emission include a multiplet of sharp peaks that exhibit a strong filling factor dependence. Spin wave measurements by resonant inelastic light scattering probe breaking of spin rotational invariance and are used to link this optical emission with collective phases of electrons. A remarkably rapid interplay between emission peak intensities manifests phase competition in the second Landau level.

Pooled influenza vaccine effectiveness estimates for Australia, 2012-2014.

Data were pooled from three Australian sentinel general practice influenza surveillance networks to estimate Australia-wide influenza vaccine coverage and effectiveness against community presentations for laboratory-confirmed influenza for the 2012, 2013 and 2014 seasons. Patients presenting with influenza-like illness at participating GP practices were swabbed and tested for influenza. The vaccination odds of patients testing positive were compared with patients testing negative to estimate influenza vaccine effectiveness (VE) by logistic regression, adjusting for age group, week of presentation and network. Pooling of data across Australia increased the sample size for estimation from a minimum of 684 to 3,683 in 2012, from 314 to 2,042 in 2013 and from 497 to 3,074 in 2014. Overall VE was 38% [95% confidence interval (CI) 24-49] in 2012, 60% (95% CI 45-70) in 2013 and 44% (95% CI 31-55) in 2014. For A(H1N1)pdm09 VE was 54% (95% CI-28 to 83) in 2012, 59% (95% CI 33-74) in 2013 and 55% (95% CI 39-67) in 2014. For A(H3N2), VE was 30% (95% CI 14-44) in 2012, 67% (95% CI 39-82) in 2013 and 26% (95% CI 1-45) in 2014. For influenza B, VE was stable across years at 56% (95% CI 37-70) in 2012, 57% (95% CI 30-73) in 2013 and 54% (95% CI 21-73) in 2014. Overall VE against influenza was low in 2012 and 2014 when A(H3N2) was the dominant strain and the vaccine was poorly matched. In contrast, overall VE was higher in 2013 when A(H1N1)pdm09 dominated and the vaccine was a better match. Pooling data can increase the sample available and enable more precise subtype- and age group-specific estimates, but limitations remain.

S-glutathionylation uncouples eNOS and regulates its cellular and vascular function.

Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O(2)(•-)), which are key mediators of cellular signalling. In the presence of Ca(2+)/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from l-arginine (l-Arg) by means of electron transfer from NADPH through a flavin containing reductase domain to oxygen bound at the haem of an oxygenase domain, which also contains binding sites for tetrahydrobiopterin (BH(4)) and l-Arg. In the absence of BH(4), NO synthesis is abrogated and instead O(2)(•-) is generated. While NOS dysfunction occurs in diseases with redox stress, BH(4) repletion only partly restores NOS activity and NOS-dependent vasodilation. This suggests that there is an as yet unidentified redox-regulated mechanism controlling NOS function. Protein thiols can undergo S-glutathionylation, a reversible protein modification involved in cellular signalling and adaptation. Under oxidative stress, S-glutathionylation occurs through thiol-disulphide exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl radicals with reduced glutathione. Cysteine residues are critical for the maintenance of eNOS function; we therefore speculated that oxidative stress could alter eNOS activity through S-glutathionylation. Here we show that S-glutathionylation of eNOS reversibly decreases NOS activity with an increase in O(2)(•-) generation primarily from the reductase, in which two highly conserved cysteine residues are identified as sites of S-glutathionylation and found to be critical for redox-regulation of eNOS function. We show that eNOS S-glutathionylation in endothelial cells, with loss of NO and gain of O(2)(•-) generation, is associated with impaired endothelium-dependent vasodilation. In hypertensive vessels, eNOS S-glutathionylation is increased with impaired endothelium-dependent vasodilation that is restored by thiol-specific reducing agents, which reverse this S-glutathionylation. Thus, S-glutathionylation of eNOS is a pivotal switch providing redox regulation of cellular signalling, endothelial function and vascular tone.

Subcutaneous phaeohyphomycosis caused by Exophiala spinifera in a European patient with lymphoma: a rare occurrence case report and literature review.

Exophiala spinifera is a dematiaceous fungus responsible for rare skin infections presenting as phaeohyphomycosis or chromoblastomycosis which has been primarily reported in tropical and subtropical areas (Asia, South and North America). We report the first case of E. spinifera phaeohyphomycosis in a European patient. The phaeohyphomycosis was limited to the skin, involving the finger of an immunocompromised patient presenting with a large B-cell lymphoma treated by R-mini-CHOP regimen. Remission was initially achieved by surgical excision; however, a local subcutaneous relapse required treatment with itraconazole. We performed a literature review of the 32 previously published cases of E. spinifera phaeohyphomycosis highlighting its clinical phenotype: disseminated infection with extracutaneous involvement and poor prognosis were reported in young patients, of whom some were recently associated with CARD9 mutations, whereas cases in older immunocompromised patients were limited to the skin and showed better prognosis. There is currently no standard treatment for E. spinifera phaeohyphomycosis; however, itraconazole, alone or in combination, allowed partial or complete response in 16 out of 20 cases.