DPP4 Inhibitor-Induced Bullous Pemphigoid in Patients with Diabetes and Chronic Kidney Disease: Clinical Case Series.

INTRODUCTION: Dipeptidyl peptidase-4 (DPP4) inhibitors (gliptins) are commonly prescribed for glucose control in patients with advanced chronic kidney disease (CKD) in whom other oral glucose-lowering agents are contraindicated. In the past few years, new reports of drug-induced bullous pemphigoid associated with DPP4 inhibitors have emerged. However, there is not enough information about the renal function of the patients with DPP4 inhibitor-induced bullous pemphigoid, and it remains unknown whether the risk of this complication is increased among patients with CKD. CASE REPORTS: Five patients with stage 3b-5 CKD received a diagnosis of DPP4 inhibitor-associated bullous pemphigoid in our institution within a period of 17 months (between December 2018 and May 2020). All patients in the current series were male. Skin biopsies were performed in all patients. Three cases were secondary to vildagliptin, and 2 cases were attributed to linagliptin. In each of these patients, treatment consisted of permanent discontinuation of the DPP4 inhibitor and administration of corticosteroids. CONCLUSION: We report here the first single-center experience of DPP4 inhibitor-induced bullous pemphigoid in patients with CKD. Our case series highlights the importance of considering bullous pemphigoid in patients with CKD taking DPP4 inhibitors presenting with bullous or pruritic cutaneous lesions. By calling attention to this important complication, we hope to minimize the delay in diagnosing DPP4 inhibitor-induced bullous pemphigoid among patients with CKD.

Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study.

Background: The aim of this study was to measure serum brain injury biomarkers in patients with COVID-19 admitted to intensive care unit (ICU), without evidence of brain impairment, and to determine potential correlations with systemic inflammatory markers, illness severity, and outcome. Methods: In patients admitted to the ICU with COVID-19, without clinical evidence of brain injury, blood S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured on admission. Clinical, routine laboratory data and illness severity were recorded. Comparisons between 28-day survivors and non-survivors and correlations of neurological biomarkers to other laboratory data and illness severity, were analyzed. Results: We included 50 patients, median age 64 [IQR 58-78] years, 39 (78%) males, 39 (78%) mechanically ventilated and 11 (22%) under high flow nasal oxygen treatment. S100B and NSE were increased in 19 (38%) and 45 (90%) patients, respectively. S100B was significantly elevated in non-survivors compared to survivors: 0.15 [0.10-0.29] versus 0.11 [0.07-0.17] µg/L, respectively, (p = 0.03), and significantly correlated with age, IL-6, arterial lactate, noradrenaline dose, illness severity and lymphocyte count. IL-6 was significantly correlated with C-reactive protein, noradrenaline dose and organ failure severity. NSE was correlated only with lactate dehydrogenase. Conclusion: Brain injury biomarkers were frequently elevated in COVID-19 ICU patients, in the absence of clinical evidence of brain injury. S100B was significantly correlated with IL-6, low lymphocyte count, hypoperfusion indices, illness severity, and short-term outcome. These findings indicate a possible brain astrocytes and neurons involvement, also suggesting a broader role of S100B in systemic inflammatory response.

Strontium isotopes and concentrations in cremated bones suggest an increased salt consumption in Gallo-Roman diet.

The high temperatures reached during cremation lead to the destruction of organic matter preventing the use of traditional isotopic methods for dietary reconstructions. Still, strontium isotope (87Sr/86Sr) and concentration ([Sr]) analyses of cremated human remains offer a novel way to assess changing consumption patterns in past populations that practiced cremation, as evidenced by a large amount of new data obtained from Metal Ages and Gallo-Roman human remains from Destelbergen, Belgium. The Gallo-Roman results show significantly higher [Sr] and a narrower interquartile range in 87Sr/86Sr (0.7093-0.7095), close to the value of modern-day seawater (0.7092). This contrasts with the Metal Ages results, which display lower concentrations and a wider range in 87Sr/86Sr (0.7094-0.7098). This typical Sr signature is also reflected in other sites and is most likely related to an introduction of marine Sr in the form of salt as a food preservative (e.g. salt-rich preserved meat, fish and fish sauce). Paradoxically, this study highlights caution is needed when using 87Sr/86Sr for palaeomobility studies in populations with high salt consumption.

These boots are made for burnin': Inferring the position of the corpse and the presence of leather footwears during cremation through isotope (δ13C, δ18O) and infrared (FTIR) analyses of experimentally burnt skeletal remains.

Cremation is a complex mortuary practice, involving a number of activities of the living towards the dead before, during, and after the destruction of the bodily soft tissues by fire. The limiting information concerning these behavioral patterns obtained from the pyre remains and/or cremation deposits prevents the reconstruction of the handling of the corpse during the burning process. This pioneering study tries to determine the initial positioning of the corpse in the pyre and assess whether the deceased was wearing closed leather shoes during cremation through isotopic (δ13C, δ18O) and infrared (ATR-FTIR) analyses of experimentally burnt pig remains, used as a proxy for humans. The results obtained show that both the position of feet on or within the pyre and the presence of footwears may moderately-to-highly influence the oxygen isotope ratios of bone apatite carbonates and the cyanamide content of calcined bone in certain situations. By forming a protective layer, shoes appear to temporarily delay the burning of the underlying pig tissues and to increase the heat-shielding effect of the soft tissues protecting the bone mineral fraction. In such case, bioapatite bone carbonates exchange oxygen with a relatively more 18O-depleted atmosphere (due to the influence of lignin-derived oxygen rather than cellulose-derived oxygen), resulting in more pronounced decrease in the δ18Ocarb values during burning of the shoed feet vs. unshoed feet. The shift observed here was as high as 2.5‰. A concomitant isotopic effect of the initial location of the feet in the pyres was also observed, resulting in a top-to-bottom decrease difference in the δ18Ocarb values of shoed feet of about 1.4‰ between each deposition level tested. Finally, the presence of cyanamide (CN/P ≥ 0.02) seems to be indicative of closed footwear since the latter creates favorable conditions for its incorporation into bone apatite.

Revisiting metric sex estimation of burnt human remains via supervised learning using a reference collection of modern identified cremated individuals (Knoxville, USA).

OBJECTIVES: This study aims to increase the rate of correctly sexed calcined individuals from archaeological and forensic contexts. This is achieved by evaluating sexual dimorphism of commonly used and new skeletal elements via uni- and multi-variate metric trait analyses. MATERIALS AND METHODS: Twenty-two skeletal traits were evaluated in 86 individuals from the William M. Bass donated cremated collection of known sex and age-at-death. Four different predictive models, logistic regression, random forest, neural network, and calculation of population specific cut-off points, were used to determine the classification accuracy (CA) of each feature and several combinations thereof. RESULTS: An overall CA of ≥ 80% was obtained for 12 out of 22 features (humerus trochlea max., and lunate length, humerus head vertical diameter, humerus head transverse diameter, radius head max., femur head vertical diameter, patella width, patella thickness, and talus trochlea length) using univariate analysis. Multivariate analysis showed an increase of CA (≥ 95%) for certain combinations and models (e.g., humerus trochlea max. and patella thickness). Our study shows metric sexual dimorphism to be well preserved in calcined human remains, despite the changes that occur during burning. CONCLUSIONS: Our study demonstrated the potential of machine learning approaches, such as neural networks, for multivariate analyses. Using these statistical methods improves the rate of correct sex estimations in calcined human remains and can be applied to highly fragmented unburnt individuals from both archaeological and forensic contexts.

Estimating age-at-death in burnt adult human remains using the Falys-Prangle method.

OBJECTIVES: The Falys-Prangle-method assesses age-related morphological changes to the sternal clavicle end (SCE), enabling the observation of mature adults from the 5th decade onwards in unburnt human skeletal remains. The aim of this study is to investigate the applicability of the Falys-Prangle-method on burnt human remains. MATERIALS AND METHODS: Fifty-two SCE of 40 cremated individuals (out of 86) from the William M. Bass collection of the Forensic Anthropology Center (Knoxville, Tennessee) of known age-at-death and sex are available for assessment. Surface topography, porosity, and osteophyte formation are evaluated, after which the calculated composite score is associated with the corresponding age range as described by Falys and Prangle. The method is also applied on an archaeological case study from Oudenburg, Belgium, dating to the Roman period. RESULTS: The assessed age ranges strongly agree with the true age ranges (α = 0.828), suggesting the Falys-Prangle-method to be applicable on burnt human remains. The case study from Oudenburg yields markedly improved age-at-death estimates, significantly enhancing our understanding of the age distribution within this community. DISCUSSION: Information on age-at-death is key in the construction of biological profiles of past individuals. The mature adult is often invisible in the archaeological record since most macroscopic age estimation methods do not distinguish beyond 46+ years old. Our study stresses the usefulness of a large-scale application of the Falys-Prangle-method, which will increase the visibility of mature adults, especially in archaeological burnt human skeletal collections, where such information is, at present, extremely difficult to obtain.

Dapagliflozin as a cause of acute tubular necrosis with heavy consequences: a case report.

A 50-year-old man with type II diabetes, hypertension and dyslipidemia, presented with non-oliguric acute kidney injury (AKI) and anemia. Renal biopsy showed acute tubular necrosis (ATN) with extensive cytoplasmic vacuolization and areas of tubulitis. These findings were ultimately attributed to dapagliflozin, which he started 3 months earlier due to poor glycemic control. ATN with similar microscopic findings has been described with larger doses of dapagliflozin in non-clinical trials. Our patient was started on dialysis and remained dialysis-dependent for 4 weeks while his renal function improved gradually thereafter. Sixteen months after initial presentation he is being followed as an outpatient with chronic kidney disease (CKD) stage 3a. Dapagliflozin belongs to a novel class of antidiabetic drugs for which clinical trials show great beneficial effects on cardiovascular outcomes and glycemic control and as with many new drugs, their safety profile is being constantly revised. We report the first biopsy-proven ATN caused by dapagliflozin. Great caution together with continuous monitoring of renal function is advised when implementing SGLT-2 inhibitors in clinical practice.

Magnesium retards the progress of the arterial calcifications in hemodialysis patients: a pilot study.

BACKGROUND: The aim of the study was to evaluate the impact of magnesium (Mg) on the evolution of arterial calcifications in hemodialysis patients. PATIENTS AND METHODS: Seventy-two stable hemodialysis patients were randomly allocated to two groups: 36 administered a regimen containing magnesium carbonate plus calcium acetate as a phosphate binder (Mg group), while the rest 36 received calcium acetate alone (Ca group). The presence and the progression of arterial calcifications were evaluated in plain X-rays using a simple vascular calcification score. The duration of the follow-up period was 12 months. RESULTS: Thirty-two patients of the Mg group and 27 of the Ca group completed the study. The mean time average values of the biochemical laboratories did not differ between the two groups, except serum Mg: 2.83 + 0.38 in the Mg group versus 2.52 + 0.27 mg/dl in the Ca group, p = 0.001. In 9/32 (28.12 %) patients of the Mg group and in 12/27 (44.44 %) patients of the Ca group, the arterial calcifications were worsened, p = 0.276. Moreover, in 4/32 (15.6 %) patients of the Mg group and in 0/27 (0 %) patients of the Ca group, they were improved, p = 0.040. The multivariate logistic regression analysis revealed that serum magnesium was an independent predictor for no progression of the arterial calcifications, p = 0.047. CONCLUSIONS: Magnesium probably retards the arterial calcifications in hemodialysis patients. Further clinical studies are needed to clarify whether magnesium provides cardiovascular protection to this group of patients.

Serum S100B protein is increased and correlates with interleukin 6, hypoperfusion indices, and outcome in patients admitted for surgical control of hemorrhage.

S100B protein, an acknowledged biomarker of brain injury, has been reported to be increased in hemorrhagic shock. Also, acute hemorrhage is associated with inflammatory response. The aim of this study was to investigate the concentrations of serum S100B and the potential relationships with interleukin 6 (IL-6), severity of tissue hypoperfusion, and prognosis in patients admitted for surgical control of severe hemorrhage. Patients undergoing elective abdominal aortic aneurysm surgery participated as control subjects. Serum samples were drawn before, at the end of surgery, and after 6 and 24 h. Sixty-four patients with severe hemorrhage (23 trauma and 41 nontrauma) and 17 control subjects were included. Increased preoperative concentrations of S100B protein (1.70 ± 2.13 and 0.81 ± 1.23 µg/L) and IL-6 (241 ± 291 and 226 ± 238 pg/mL) were found in patients with traumatic and nontraumatic reason, respectively, and remained elevated throughout 24 h. Compared with nontrauma, trauma patients exhibited higher preoperative S100B levels (P < 0.05). Overall mortality was 47%. In control subjects, preoperative S100B and IL-6 levels were within normal limits and increased at the end of surgery (P < 0.001 and P < 0.01, respectively). Preoperative S100B correlated with IL-6 (r = 0.78, P < 0.01), arterial lactate (r = 0.50, P < 0.01), pH (r = -0.45, P < 0.01), and bicarbonate (r = -0.40, P < 0.01). Multiple analysis revealed that preoperative S100B in trauma and lactate in nontrauma patients were independently associated with outcome. In predicting death, preoperative S100B yielded receiver operator characteristics curve areas of 0.75 for all patients and 0.86 for those with trauma. These results indicate that severe hemorrhage in patients without brain injury is associated with increased serum levels of S100B, which correlates with IL-6 and tissue hypoperfusion. Moreover, the predictive ability of S100B for mortality, suggests that it could be a marker of potential clinical value in identifying, among patients with severe hemorrhage, those at greater risk for adverse outcome.