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Factors responsible for difficult to treat superficial fungal infections: A study from a tertiary healthcare center in India

Mycoses. 2021 May 9. doi: 10.1111/myc.13301. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent and clinically unresponsive dermatophytosis is being increasingly observed in India. However, there is little information regarding the extent of the problem and the factors responsible for these difficult to treat superficial fungal infections.

AIM: To identify factors contributing to difficult to treat recurrent superficial fungal infections.

MATERIALS AND METHODS: This prospective cross-sectional study enrolled 105 patients of all age groups presenting with either recurrent or long-standing dermatophyte infection attending the out-patient department of Dermatology, Venerology and Leprosy of Bharati Hospital, Pune, India between September 2018 to March 2020. Patients were clinically examined, clinical history was taken, and questions were asked regarding their current complaints and recorded in a proforma. Data were analysed using the SPSS software package.

RESULTS: The males outnumbered females (74.3% vs 25.7 %). A strong association was observed between the presence of past history and duration of disease (p=0.007). The association of use of topical steroids or keratolytic agents with the duration of disease was statistically significant (p=0.022). There was a statistically significant inverse association of duration of disease with dermatologist consultation (p<0.001). The association between consultation with non-dermatologist and the duration of disease was statistically significant (p=0.035).

CONCLUSION: Hyperhidrosis, obesity, positive family history, tight clothing, and chronic diseases may be considered important factors in acquiring dermatophytic infection. However, when it comes to difficult to treat tinea infections, irrational usage of topical steroids, treatment from non-dermatologists, and a past history of tinea appear to be more critical causative factors. Treatment of dermatophytosis by dermatologists/ trained physicians and increasing general awareness of the public regarding the current situation about tinea in the country would help to alleviate the current crisis.

PMID:33966290 | DOI:10.1111/myc.13301

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Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma

Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

METHODS: We identified all patients diagnosed with MM in Sweden from January 1st , 1958 to December 31st , 2011. A total of 26,627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis.

RESULTS: The cumulative melphalan exposure was significantly higher (OR=2.8, 95% CI 1.7-5.2; p<0.001) among cases (median 988 mg; IQR 644-1,640) compared to controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8 – 5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy.

CONCLUSION: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks.

PMID:33966293 | DOI:10.1111/ejh.13650

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The Changes in Brain Oxygenation During Transcranial Alternating Current Stimulation as Consequences of Traumatic Brain Injury: A Near-Infrared Spectroscopy Study

Adv Exp Med Biol. 2021;1269:235-239. doi: 10.1007/978-3-030-48238-1_37.

ABSTRACT

The aim was to evaluate the changes in brain tissue oxygenation, assessed by near-infrared spectroscopy (NIRS), during transcranial alternating current stimulation (tACS) in patients with mild and moderate traumatic brain injury (TBI). Nineteen patients with diffuse, blunt, non-severe TBI (mean age 32.7 ± 11.4 years; 4 women and 15 men; Glasgow Coma Score before tACS 14.1 ± 0.5) were treated by 10 Hz in-phase tACS applied for 30 minutes to the left and right lateral prefrontal cortex at 21 days after TBI. Regional cerebral tissue oxygen saturation (SctO2) in the frontal lobes was measured simultaneously by the cerebral oximeter. Significance was preset to P < 0.05. The SctO2 values before tACS were not different between hemispheres ~65%. After 15 minutes of tACS, a significant (p < 0.05) decrease in regional SctO2 was observed with the minimum at the eighth minute of 53.4 ± 3.2% and 53.4 ± 3.2% in the left and right hemispheres, respectively. At the end of the stimulation (30 minutes), the hemispheric differences in cerebral oxygen saturation became statistically insignificant again (p > 0.05). Therefore, tACS causes a significant decrease in SctO2, probably, due to neuronal activation. Our data indicate that tACS may need to be supplemented with oxygen therapy. Further research is required.

PMID:33966223 | DOI:10.1007/978-3-030-48238-1_37

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Addition of Drag-Reducing Polymers to Colloid Resuscitation Fluid Enhances Cerebral Microcirculation and Tissue Oxygenation After Traumatic Brain Injury Complicated by Hemorrhagic Shock

Adv Exp Med Biol. 2021;1269:283-288. doi: 10.1007/978-3-030-48238-1_45.

ABSTRACT

Hemorrhagic shock (HS) is a severe complication of traumatic brain injury (TBI) that doubles mortality due to severely compromised microvascular cerebral blood flow (mvCBF) and oxygen delivery reduction, as a result of hypotension. Volume expansion with resuscitation fluids (RF) for HS does not improve microvascular CBF (mvCBF); moreover, it aggravates brain edema. We showed that the addition of drag-reducing polymers (DRP) to crystalloid RF (lactated Ringer’s) significantly improves mvCBF, oxygen supply, and neuronal survival in rats suffering TBI+HS. Here, we compared the effects of colloid RF (Hetastarch) with DRP (HES-DRP) and without (HES). Fluid percussion TBI (1.5 ATA, 50 ms) was induced in rats and followed by controlled HS to a mean arterial pressure (MAP) of 40 mmHg. HES or HES-DRP was infused to restore MAP to 60 mmHg for 1 h (prehospital period), followed by blood reinfusion to a MAP of 70 mmHg (hospital period). In vivo two-photon microscopy was used to monitor cerebral microvascular blood flow, tissue hypoxia (NADH), and neuronal necrosis (i.v. propidium iodide) for 5 h after TBI+HS, followed by postmortem DiI vascular painting. Temperature, MAP, blood gases, and electrolytes were monitored. Statistical analyses were done using GraphPad Prism by Student’s t-test or Kolmogorov-Smirnov test, where appropriate. TBI+HS compromised mvCBF and tissue oxygen supply due to capillary microthrombosis. HES-DRP improved mvCBF and tissue oxygenation (p < 0.05) better than HES. The number of dead neurons in the HES-DRP was significantly less than in the HES group: 76.1 ± 8.9 vs. 178.5 ± 10.3 per 0.075 mm3 (P < 0.05). Postmortem visualization of painted vessels revealed vast microthrombosis in both hemispheres that were 33 ± 2% less in HES-DRP vs. HES (p < 0.05). Thus, resuscitation after TBI+HS using HES-DRP effectively restores mvCBF and reduces hypoxia, microthrombosis, and neuronal necrosis compared to HES. HES-DRP is more neuroprotective than lactated Ringer’s with DRP and requires an infusion of a smaller volume, which reduces the development of hypervolemia-induced brain edema.

PMID:33966231 | DOI:10.1007/978-3-030-48238-1_45

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The relationship between the severity and mortality of SARS-CoV-2 infection and 25-hydroxyvitamin D concentration – a metaanalysis

Adv Respir Med. 2021;89(2):145-157. doi: 10.5603/ARM.a2021.0037.

ABSTRACT

INTRODUCTION: There is increasing scientific interest in the possible association between hypovitaminosis D and the risk of SARS-CoV-2 infection severity and/or mortality.

OBJECTIVE: To conduct a metanalysis of the association between 25-hydroxyvitamin D (25(OH)D) concentration and SARS-CoV-2 infection severity or mortality.

MATERIAL AND METHODS: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for studies published between December 2019 and December 2020. Effect statistics were pooled using random effects models. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Targeted outcomes: mortality and severity proportions in COVID-19 patients with 25(OH)D deficiency, defined as serum 25(OH)D < 50 nmol/L.

RESULTS: In the 23 studies included (n = 2692), the mean age was 60.8 (SD ± 15.9) years and 53.8% were men. Results suggested that vitamin 25(OH)D deficiency was associated with increased risk of severe SARS-CoV-2 disease (RR 2.00; 95% CI 1.47-2.71, 17 studies) and mortality (RR 2.45; 95% CI 1.24-4.84, 13 studies). Only 7/23 studies reported C-reactive protein values, all of which were > 10 mg/L. Conclusions 25(OH)D deficiency seems associated with increased SARS-CoV-2 infection severity and mortality. However, findings do not imply causality, and randomized controlled trials are required, and new studies should be designed to determine if decreased 25(OH)D is an epiphenomenon or consequence of the inflammatory process associated with severe forms of SARS-CoV-2. Meanwhile, the concentration of 25(OH)D could be considered as a negative acute phase reactant and a poor prognosis in COVID-19 infection.

PMID:33966262 | DOI:10.5603/ARM.a2021.0037

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Impact of Including Carer Information in Time Trade-Off Tasks: Results from a Pilot Study

Pharmacoecon Open. 2021 May 9. doi: 10.1007/s41669-021-00270-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Carer quality of life (QoL) can be included in economic evaluations and captured using EQ-5D. Traditional valuation tasks require participants to imagine living in a health state for a number of years, without being told what to consider. This pilot study sought to investigate whether participants implicitly consider the impact of the health state on others, and the extent to which this may impact health state valuations.

METHODS: Composite time trade-off (TTO) interviews were conducted with a convenience sample. Each interview included a ‘traditional’ TTO exercise to value three health states, and a ‘combined’ TTO exercise, where participants valued the same health states again, having been informed that they would require a carer living in a particular health state. Qualitative feedback was collected after each exercise. Paired t-test comparisons of the utilities elicited in each exercise were made.

RESULTS: Thirty-three participants enrolled in the pilot. Mean differences between exercises were not statistically significant and differed in direction, although considerable heterogeneity was observed in individual response trajectories. Overall, 36% (n = 12) of participants expressed an unprompted concern about being a burden on others in the traditional exercise, and 67% (n = 22) of participants would have responded differently had the carer been in full health in the combined exercise.

CONCLUSION: Providing contextual information about carers may impact valuations. Further research is required to better understand the reasons behind the variation in individual response trajectories observed in this pilot study. The insights from this study may be useful for informing the design of related future studies.

PMID:33966180 | DOI:10.1007/s41669-021-00270-x

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Comparison of survival outcomes for axillary surgery extent based on intraoperative sentinel lymph node biopsy result after neoadjuvant chemotherapy for breast cancer

Breast Cancer Res Treat. 2021 May 8. doi: 10.1007/s10549-021-06249-w. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC).

METHOD: We retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n = 188) and ALND (n = 295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups.

RESULT: At a median follow-up of 59.4 months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.43-2.05, p = 0.876) and 5-year overall survival (97.7% vs. 97.3%, HR = 1.65, 95% CI = 0.58-4.65, p = 0.347) between the two groups.

CONCLUSION: Our analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

PMID:33966181 | DOI:10.1007/s10549-021-06249-w

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Signal Detection in EUROmediCAT: Identification and Evaluation of Medication-Congenital Anomaly Associations and Use of VigiBase as a Complementary Source of Reference

Drug Saf. 2021 May 9. doi: 10.1007/s40264-021-01073-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications.

AIMS: This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals.

METHODS: Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation.

RESULTS: EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly.

CONCLUSION: EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.

PMID:33966183 | DOI:10.1007/s40264-021-01073-z

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Choroidal thickness changes in children with chronic heart failure due to dilated cardiomyopathy

Int Ophthalmol. 2021 May 9. doi: 10.1007/s10792-021-01774-5. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate choroidal thickness (CTh) in children with chronic heart failure (CHF) secondary to dilated cardiomyopathy (DCM) using spectral domain optical coherence tomography (SD-OCT) and to compare their values to those of healthy children.

METHODS: Sixty eyes of thirty children (mean age 9.9 ± 3.57 years) with chronic heart failure (left ventricular ejection fraction, LVEF ≤ 55%) due to DCM lasting for over 6 months were prospectively enrolled. The control group consisted of 30 age- (mean age 10.16 ± 3.42 years) and sex-matched healthy children. All participants underwent transthoracic echocardiography with LVEF measured using the Simpson method and had the blood serum level of N-terminal-pro-brain natriuretic peptide marker (NT-proBNP) determined. All children underwent SD-OCT and had subfoveal choroidal thickness (SFCTh) and CTh measured at 1500 µm (μm) nasally, temporally, superiorly and inferiorly from the fovea in both eyes by two investigators.

RESULTS: CTh at all locations was statistically significantly lower in children with DCM compared to the control group. Mean CTh in the group with CHF compared to the control group were (304.03 vs. 369.72 μm, p < 0.05) at the subfoveal location, (245.87 vs. 284 μm, p < 0.05) 1500 μm nasally from the fovea, (291.5 vs. 355.95 μm, p < 0.05) 1500 μm temporally from the fovea, (303.98 vs. 357.58 μm, p < 0.05) 1500 μm superiorly from the fovea and (290.92 vs. 344.96 μm, p < 0.05) 1500 μm inferiorly from the fovea. The average difference CTh between the study groups ranged from 38.13 to 65.69 μm at individual locations. In both groups, CTh was the thickest at subfoveal location (304.03 vs. 369.72 μm, p < 0.05) and the thinnest was 1500 μm nasally from the fovea (262.37 vs. 336.87 μm, p < 0.05). There was no correlation between CTh and age, gender, biometry and refractive error. No correlation was found between CTh and LVEF and NT-proBNP.

CONCLUSION: Patients with CHF due to DCM had a thinner CTh at all measured locations. The results of our research indicate that CHF affects CTh and this parameter may be very helpful in monitoring the clinical course of the disease in children with DCM.

PMID:33966146 | DOI:10.1007/s10792-021-01774-5

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A Model-Strengthened Imaging Biomarker for Survival Prediction in EGFR-Mutated Non-small-cell Lung Carcinoma Patients Treated with Tyrosine Kinase Inhibitors

Bull Math Biol. 2021 May 8;83(6):68. doi: 10.1007/s11538-021-00902-7.

ABSTRACT

Non-small-cell lung carcinoma is a frequent type of lung cancer with a bad prognosis. Depending on the stage and genomics, several therapeutical approaches are used. Tyrosine Kinase Inhibitors (TKI) may be successful for a time in the treatment of EGFR-mutated non-small cells lung carcinoma. Our objective is here to introduce a survival assessment as their efficacy in the long run is challenging to evaluate. The study includes 17 patients diagnosed with EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI with 3 computed tomography (CT) scans of the primary tumor (one before the TKI introduction and two after). An imaging biomarker based on evolution of texture heterogeneity between the first and the third exams is derived and computed from a mathematical model and patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker ([Formula: see text]). Using the ROC curve, the patients are separated into two populations and the comparison of the survival curves is statistically significant ([Formula: see text]). The baseline exam seems to have a significant role in the prediction of response to TKI treatment. More precisely, our imaging biomarker defined using only the CT scan before the TKI introduction allows to determine a first classification of the population which is improved over time using the imaging marker as soon as more CT scans are available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor.

PMID:33966172 | DOI:10.1007/s11538-021-00902-7