Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir/tenofovir alafenamide/emtricitabine: case report and review of the literature.

OBJECTIVES: The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC/FTC/TAF. METHODS: Clinical case report and review of the literature. RESULTS: A heavily treatment-experienced patient was switched to BIC/FTC/TAF due to drug-drug interactions after being diagnosed with disseminated Mycobacterium avium-intracellulare disease. He had been treated before with raltegravir with poor adherence. No mutations in the integrase gene were detected 1 year after finishing treatment with raltegravir. Months after being switched to BIC/FTC/TAF, and again with poor adherence documented, virological failure (VF) was detected. The polymorphic substitution E157Q and the resistance mutation R263K in the integrase gene were detected, as well as M184V, among other mutations in the reverse transcriptase gene. The patient is currently being treated with dolutegravir q12h plus boosted darunavir along with directly observed treatment, and for the first time in 20 years, plasmatic viral load values are below 100 copies/mL. CONCLUSIONS: This case illustrates that the combination of E157Q and R263K plus M184V can be selected in vivo in a clinical scenario of poor adherence with BIC/FTC/TAF, although it is a very rare phenomenon. Previous VF with first-generation integrase strand transfer inhibitors (INSTIs) should be kept in mind when switching patients to second-generation INSTIs.

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy.

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. METHODS: The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. RESULTS: Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. CONCLUSION: Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. REGISTRATION: ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036 .

Clonal spread of fluconazole-resistant C. parapsilosis in patients admitted to a referral hospital located in Burgos, Spain, during the COVID-19 pandemic.

BACKGROUND: Fluconazole-resistant Candida parapsilosis (FRCP) is a matter of concern in Spain. OBJECTIVES: We here report a FRCP spread across a 777-bed referral hospital located in Burgos, Spain, during the COVID-19 pandemic. PATIENTS/METHODS: In April 2021, an FRCP isolate (MIC = 64 mg/L, E-test®) from a hospitalised patient was detected. Up to June 2022, all C. parapsilosis isolates (n = 35) from hospitalised patients (n = 32) were stored and genotyped using microsatellite markers, and their antifungal susceptibilities were studied (EUCAST); FRCP isolates were molecularly characterised. RESULTS: We detected 26 FRCP isolates collected between 2021 (n = 8) and 2022 (n = 18); isolates were susceptible to amphotericin B, echinocandins and ibrexafungerp. FRCP isolates were grouped into three genotypes: CP-707 and CP-708 involved isolates harbouring the Y132F + R398I ERG11p substitutions (n = 24) and were clonally related; the remaining CP-675 genotype involved isolates harbouring the G458S ERG11p substitution (n = 2). FRCP genotypes were genetically related to the FRCP genotypes found in Madrid and were unrelated to fluconazole-susceptible ones. Patients harbouring FRCP were mainly (n = 22/23) admitted to intensive care units. Most patients had received broad-spectrum antibiotics (n = 22/23), and/or antifungal therapy with azoles (n = 14/23) within the 30 days prior to FRCP isolation. Thirteen patients were colonised, 10 of whom were infected and presented candidaemia (n = 8/10), endovascular infection (n = 1/10) or complicated urinary infection (n = 1/10). Overall nonattributable 30-day mortality was 17% (n = 4/23). CONCLUSIONS: We report an outbreak caused by FRCP affecting patients admitted to the ICU of a referral hospital located in Burgos. Patients harbouring FRCP had a higher fluconazole use than those carrying susceptible isolates.

RNA Expression of MMP12 Is Strongly Associated with Inflammatory Bowel Disease and Is Regulated by Metabolic Pathways in RAW 264.7 Macrophages.

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including inflammatory bowel disease. Although previously published data suggested that the modulation of MMP12 in macrophages could be a determinant for the development of intestinal inflammation, scarce information is available on the mechanisms underlying the regulation of MMP12 expression in those phagocytes. Therefore, in this study, we aimed to delineate the association of MMP12 with inflammatory bowel disease and the molecular events leading to the transcriptional control of this metalloproteinase. For that, we used publicly available transcriptional data. Also, we worked with the RAW 264.7 macrophage cell line for functional experiments. Our results showed a strong association of MMP12 expression with the severity of inflammatory bowel disease and the response to relevant biological therapies. In vitro assays revealed that the inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and the stimulation of the AMP-activated protein kinase (AMPK) signaling pathway potentiated the expression of Mmp12. Additionally, AMPK and mTOR required a functional downstream glycolytic pathway to fully engage with Mmp12 expression. Finally, the pharmacological inhibition of MMP12 abolished the expression of the proinflammatory cytokine Interleukin-6 (Il6) in macrophages. Overall, our findings provide a better understanding of the mechanistic regulation of MMP12 in macrophages and its relationship with inflammation.

Enhancing estimation methods for integrating probability and nonprobability survey samples with machine-learning techniques. An application to a Survey on the impact of the COVID-19 pandemic in Spain.

Web surveys have replaced Face-to-Face and computer assisted telephone interviewing (CATI) as the main mode of data collection in most countries. This trend was reinforced as a consequence of COVID-19 pandemic-related restrictions. However, this mode still faces significant limitations in obtaining probability-based samples of the general population. For this reason, most web surveys rely on nonprobability survey designs. Whereas probability-based designs continue to be the gold standard in survey sampling, nonprobability web surveys may still prove useful in some situations. For instance, when small subpopulations are the group under study and probability sampling is unlikely to meet sample size requirements, complementing a small probability sample with a larger nonprobability one may improve the efficiency of the estimates. Nonprobability samples may also be designed as a mean for compensating for known biases in probability-based web survey samples by purposely targeting respondent profiles that tend to be underrepresented in these surveys. This is the case in the Survey on the impact of the COVID-19 pandemic in Spain (ESPACOV) that motivates this paper. In this paper, we propose a methodology for combining probability and nonprobability web-based survey samples with the help of machine-learning techniques. We then assess the efficiency of the resulting estimates by comparing them with other strategies that have been used before. Our simulation study and the application of the proposed estimation method to the second wave of the ESPACOV Survey allow us to conclude that this is the best option for reducing the biases observed in our data.

Hoarding behaviour: special features and complications in real-world clinical practice.

OBJECTIVE: Hoarding behaviour is a common but poorly characterised problem in real-world clinical practice. Although hoarding behaviour is the key component of Hoarding Disorder (HD), there are people who exhibit hoarding behaviour but do not suffer from HD. The aim of the present study was to characterise a clinical sample of patients with clinically relevant hoarding behaviour and evaluate the differential characteristics between patients with and without HD. METHODS: This study included patients who received treatment at the home visitation program in Barcelona (Spain) from January 2013 through December 2020, and scored ≥ 4 on the Clutter Image Rating scale. Sociodemographic, DSM-5 diagnosis, clinical data and differences between patients with and without an HD diagnosis were assessed. RESULTS: A total of 243 subjects were included. Hoarding behaviour had been unnoticed in its early stages and the median length in the sample was 10 years (IQR 15). 100% of the cases had hoarding-related complications. HD was the most common diagnosis in 117 patients (48.1%). CONCLUSIONS: The study found several differential characteristics between patients with and without HD diagnosis. Alcohol use disorder could play an important role among those without HD diagnosis. Home visitation programs could improve earlier detection, preventing hoarding-related complications.

Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution.

BACKGROUND: We analyzed humoral and cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in people with human immunodeficiency virus (HIV; PWH) who had CD4+ T-cell counts <200/µL (HIV<200 group). METHODS: This prospective cohort study included 58 PWH in the HIV<200 group, 36 with CD4+ T-cell counts >500/µL (HIV>500 group), and 33 HIV-1-negative controls (control group). Antibodies against the SARS-CoV-2 spike protein (anti-S immunoglobulin [Ig] G) and the receptor-binding domain (anti-RBD IgG) were quantified before and 4 weeks after the first and the second doses of BNT162b2 or mRNA-1273 (at week 8). Viral neutralization activity and T-cell responses were also determined. RESULTS: At week 8, anti-S/anti-RBD IgG responses increased in all groups (P < .001). Median (interquartile range) anti-S and anti-RBD IgG levels at week 8 were 153.6 (26.4-654.9) and 171.9 (61.8-425.8) binding antibody units (BAU)/mL, respectively, in the HIV<200 group, compared with 245.6 (145-824) and 555.8 (166.4-1751) BAU/mL in the HIV>500 group and 274.7 (193.7-680.4) and 281.6 (181-831.8) BAU/mL in controls (P < .05). Neutralizing capacity and specific T-cell immune responses were absent or reduced in 33% of those in the HIV<200 group, compared with 3.7% in the HIV>500 group (P < .01). CONCLUSIONS: One-third of PWH with CD4+ T-cell counts <200/µL show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2, and no vaccine-induced T cells after receiving coronavirus disease 2019 mRNA vaccines.

The effects of training based on Nordic hamstring and sprint exercises on measures of physical fitness and hamstring injury prevention in U19 male soccer players.

This study analysed the effects of a training program based on Nordic hamstring and sprint exercises on physical performance and hamstring injuries in young male soccer players. Forty-nine U19 players were randomly assigned to a control (CG; n = 26) or experimental group (EG; n = 23). Linear sprint and with change of direction (COD) were assessed before and after a 14-week training period. Hamstring injuries were collected during the intervention period. Between-groups analysis revealed differences in linear sprint performance (p = 0.012-0.001) in favour of the EG. Pre-to-post performance increased significantly in the EG for 20 m (effect size [ES] = -0.56) and 30 m (ES = -0.62) sprints, but a significant reduction in some COD parameters was observed (ES = 0.45-0.57). In CG, only a significant reduction in COD with dominant leg was found (ES = 0.63). Significant differences in injury burden in favour of the EG was reported such as (27.87 [CG] vs. 3.82 [EG] absence days/1000 h of exposure, rate ratio = 7.30, 95% CI 3.34-15.99). While injury incidence was not different between the EG and CG. These findings suggest that the training program implemented can improve sprint performance and reduce injury burden.

Effects of body mass-based resistance training on measures of physical fitness and musculotendinous injury incidence and burden in U16 male soccer players.

This study examined the effects of body mass-based resistance training (bmRT) on selected measures of physical fitness and injury incidence and burden in soccer players. Forty-six U16 male soccer players were randomly assigned to an control (CG; n = 26) or experimental group (EG; n = 20) Countermovement jump (CMJ), change of direction (CoD) (i.e., 20 m with one CoD), and linear sprint over 30 m were assessed before and after a 15-weeks training. Any type of musculotendinous injury that occurred throughout the intervention period was recorded. Between-group difference was noted at post-test for CMJ (p = 0.008). Pre-to-post training values increased in the EG (effect size [ES] = 1.01) while in the CG no pre-to-post changes were detected (ES = 0.27). No between-group differences at post-test were observed for sprint and CoD tests. Differences in injury burden were reported (33.28 [CG] vs. 9.55 [EG] absence days/1,000 hours exposure, rate ratio = 3.49, 95% CI 2.03-6.00, p < 0.001), but not in injury incidence. A bmRT programis suitable for improving jumping height but not linear and CoD speed performance. Additionally, bmRT may reduce injury burden, and therefore, the severity of musculotendinous injuries in U16 male soccer players.

Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function.

Skin integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. While interfollicular epidermal progenitors control normal homeostasis, hair follicle stem cells residing within the bulge provide regenerative potential during hair cycle and in response to wounding. The aryl hydrocarbon receptor (AhR) modulates cell plasticity and differentiation and its overactivation results in severe skin lesions in humans. However, its physiological role in skin homeostasis and hair growth is unknown. Reconstitution assays grafting primary keratinocytes and dermal fibroblasts into nude mice and 3-D epidermal equivalents revealed a positive role for AhR in skin regeneration, epidermal differentiation, and stem cell maintenance. Furthermore, lack of receptor expression in AhR-/- mice delayed morphogenesis and impaired hair regrowth with a phenotype closely correlating with a reduction in suprabasal bulge stem cells (α6low CD34+ ). Moreover, RNA-microarray and RT-qPCR analyses of fluorescence-activated cell sorting (FACS)-isolated bulge stem cells revealed that AhR depletion impaired transcriptional signatures typical of both epidermal progenitors and bulge stem cells but upregulated differentiation markers likely compromising their undifferentiated phenotype. Altogether, our findings support that AhR controls skin regeneration and homeostasis by ensuring epidermal stem cell identity and highlights this receptor as potential target for the treatment of cutaneous pathologies.

Association between urinary sodium excretion and hard outcomes in non-dialysis chronic kidney disease patients.

BACKGROUND: Restriction of sodium intake is routinely recommended for patients with chronic kidney disease (CKD). Whether or not sodium intake is associated with the progression of CKD and mortality remains uncertain. We evaluated the association between urinary sodium excretion (as a surrogate for sodium intake) with the occurrence of renal failure and mortality in patients with non-dialytic CKD. METHODS: We conducted a retrospective study of patients followed at a CKD clinic care hospital from October 2006 to March 2017. Adult patients with non-dialytic CKD were included. Using a time-to-event analysis, we examined the association of urinary sodium excretion as a categorical variable (categorized as quintiles: 1st quintile: 0.54-2.51 g; 2nd quintile: 2.52-3.11 g, 3rd quintile: 3.12-3.97 g, 4th quintile: 3.98-5.24 g and 5th quintile: 5.26-13.80 g) and the outcomes of interest. The primary outcome was defined as progression to end-stage renal disease requiring any type of renal replacement therapy. The secondary outcome was mortality. RESULTS: Two hundred five patients were included in the study (mean follow up of 2.6 years) with a mean eGFR of 26 (19-41) ml/min/1.73m2. 37 patients (18%) required renal replacement therapy and 52 (25,3%) died. There was association between urinary sodium excretion and need for renal replacement therapy (adjusted HR 0.245; 95%CI 0.660-0.912). There was no association between urinary sodium excretion and mortality in adjusted models. CONCLUSION: Moderate sodium intake was associated with a lower risk of renal failure.

Burden and satisfaction experienced in relatives and patients during home hospitalisation in psychiatry.

The role of caregivers is essential during home hospitalization since they act as co-therapists, being the level of responsibility experienced by them higher than usual.

The effects of jump training on measures of physical performance, lower extremities injury incidence and burden in highly trained male soccer players.

This study aimed to analyse the effects of a 16-week jump training program on the physical performance and lower extremities injury profile in semi-professional male soccer players. Participants were randomly assigned to the control group (CG; n = 13; age = 21.7 ± 3.6 years) or the experimental group (EG; n = 10; age = 22.3 ± 3.5 years). Countermovement jump (CMJ) height (cm), 30 m linear sprint time (s) with split times at 10 m and 20 m distances, and change of direction speed (CODS; 10 + 10 m with 90° turn) time (s) with turns using the dominant or non-dominant leg, were assessed before and after the intervention. Lower extremity injuries sustained throughout the intervention period were collected. Significant within-group improvements were found in EG in CMJ (p = 0.01; effect size [ES] = 1.03; large). Additionally, between-group difference after intervention was found in CMJ (F = 4.42; p = 0.013) in favour of EG. Injury burden was 194.86 (CG) vs 71.37 (EG) days of absence/1,000 h (RR = 2.73; 95% CI 2.10-3.54; p < 0.001). No other significant within-group or between-group differences were found. In conclusion, compared to regular soccer training, jump training was effective to improve jumping ability and burden in soccer players.

Clinical profile and predictors of in-hospital mortality among older patients hospitalised for COVID-19.

BACKGROUND: the coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients. METHODS: post hoc analysis of the international, multicentre, 'real-world' HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65-74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality. RESULTS: about, 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71-83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidaemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P < 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8.06), peripheral oxygen saturation at admission <92% (OR 5.85), severe lymphopenia (<500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) >1 (OR 8.31) to be independent predictors of mortality. CONCLUSION: patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation <92%, severe lymphopenia and qSOFA scale >1 were independent predictors of mortality in this population.

High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients.

OBJECTIVE: Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. METHODS: Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 µg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. RESULTS: Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104-335) and 331 (140-476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. CONCLUSION: Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.

Type V aplasia cutis congenita in a preterm newborn successfully resolved.

Aplasia cutis congenita (ACC) associated with fetus papyraceus is a rare subtype of aplasia cutis categorized as type V in Frieden's classification. It is characterized by stellate lesions in a symmetrical distribution over the trunk and proximal extremities. Conservative treatment is recommended, but there is not a well-defined therapeutic protocol. We report the case of a type V ACC in a preterm male newborn with lesions on the trunk and scalp successfully treated with topical 1% silver sulfadiazine and petrolatum gauze with an excellent evolution. This case associates a severe affectation of the scalp which represents a rare variant of type V ACC.

Levetiracetam-induced pediatric toxic epidermal necrolysis successfully treated with etanercept.

Successful management of toxic epidermal necrolysis (TEN) with tumor necrosis factor-α inhibitors has been described in adults, but few cases have been reported in children. To date, only four pediatric cases of TEN treated with infliximab and one with etanercept have been published. We present the case of an 8-year-old boy diagnosed with TEN induced by levetiracetam, successfully treated with etanercept, systemic corticosteroids, and intravenous immunoglobulin.

Association between vitamin D levels and mortality in hemodialysis patients: a cohort study.

Introduction: Low vitamin D levels are associated with mortality in hemodialysis (HD) patients; however, the serum vitamin D thresholds are unclear. This study aimed to identify the vitamin D level below which mortality increases in HD patients.Methods: A cohort of HD patients enrolled from January 2014 to January 2017 was evaluated. The variables were analyzed according to the season, namely, summer, winter, and annual average, mortality was the primary outcome. The patients were assigned to vitamin D quintiles, and multivariate Cox regression analysis adjusted for age, ethnicity, gender, body mass index (BMI), inhibitors of the renin-angiotensin system, statin, calcitriol, and antiplatelet drugs use, hemodialysis vintage, hypertension, diabetes mellitus, atherosclerotic disease, and C-reactive protein was performed.Results: There were studied 306 patients. Vitamin D levels of 18.0-23.6 ng/mL (hazard ratio [HR] = 4.30; 95% confidence interval [CI] 1.60-11.54, p = 0.004) and <18.0 ng/mL (HR = 3.83; 95% CI: 1.42-10.35, p = 0.008) in summer and vitamin D levels of 21.5-27.1 ng/mL (HR = 3.70; 95% CI: 1.50-9.11, p = 0.004) and ≤17.5 ng/mL (HR = 2.84; 95% CI: 1.13-7.13, p = 0.026) in winter were associated with mortality. The average annual values of vitamin D associated with all-cause mortality were <17.7 ng/dL (adjusted HR = 4.25, 95% CI: 1.57-11.48, p = 0.004), and between >17.7 ng/dL and ≤23.1 ng/dL (adjusted HR = 3.91, 95% CI: 1.47-10.42, p = 0.006).Conclusions: Annual average vitamin D levels <23.1 ng/mL were associated with higher all-cause mortality, regardless of the confounding variables evaluated.

Subcutaneous fat necrosis of the newborn: clinical and histopathological review and use of cutaneous ultrasound Necrosis grasa subcutánea del recién nacido: revisión clínica e histopatológica y utilidad de la ecografía cutánea.

Subcutaneous fat necrosis of the newborn is a rare lobular panniculitis. It is characteristic of term or post-term neonates with a history of perinatal compromise or maternal gestational pathology. The cutaneous manifestations consist of erythematous and indurated subcutaneous plaques and nodules located over the dorsal region and the shoulders. Diagnosis is clinical and pathological. Histopathological findings include lobular panniculitis with a lymphohistiocytic inflammatory infiltrate with few neutrophils, fatty necrosis, deposition of radial needle-shaped crystals in the adipocytes, and possible calcification and hemorrhage. The cutaneous ultrasound shows hyperechoic and avascular subcutaneous cellular tissue and acoustic shadows may appear corresponding to calcifications. The clinical differential diagnosis includes sclerema neonatorum and post-corticosteroid panniculitis. Histologically crystal-forming panniculitis conditions are in the differential diagnosis. The disease is usually self-limited but complications such as hypercalcemia, hypoglycemia, hypertriglyceridemia, thrombocytopenia, and anemia may occur. Complications should be ruled out and treated at diagnosis and during follow-up. The most important complication is hypercalcemia.La necrosis grasa subcutánea neonatal es una paniculitis lobulillar infrecuente. Es característica de neonatos a término o postérmino con antecedentes de sufrimiento perinatal o patología gestacional materna. Las manifestaciones cutáneas consisten en placas y nódulos subcutáneos eritematosos e indurados localizados preferentemente en la región dorsal y los hombros. El diagnóstico es clínicopatológico. Los hallazgos histopatológicos comprenden una paniculitis lobulillar con un infiltrado inflamatorio linfohistiocitario con escasos neutrófilos, necrosis grasa, depósito de cristales radiados en los adipocitos y posibles focos de calcificación y hemorragia. En la ecografía cutánea se observa hiperecogenicidad y avascularización del tejido celular subcutáneo y pueden aparecer sombras acústicas posteriores que se correspondencon calcificaciones. El diagnóstico diferencial clínico se debe realizar con el escleredema neonatorum y la paniculitis postesteroidea, e histológicamente con las paniculitis con formación de cristales. La enfermedad suele ser autolimitada pero pueden aparecer complicaciones como la hipercalcemia, la hipoglucemia, la hipertrigliceridemia, latrombocitopenia y la anemia. Las complicaciones deben ser descartadas y tratadas en el diagnóstico y durante el seguimiento. La complicación másimportante es la hipercalcemia.