Diagnosis and prognosis of acute respiratory distress syndrome related to diffuse pneumonic-type adenocarcinoma: a single-center case series study

BackgroundThe absence of diagnosis of acute respiratory distress syndrome (ARDS) concerns 20% of cancer patients and is associated with poorer outcomes. Diffuse pneumonic-type adenocarcinoma (P-ADC) is part of these difficult-to-diagnose ARDS, but only limited data are available regarding critically ill patients with diffuse P-ADC. We sought to describe the diagnosis process and the prognosis of P-ADC related ARDS patients admitted to the intensive care unit (ICU).MethodsSingle-center observational case series study. All consecutive patients admitted to the ICU over a two-decade period presenting with (I) histologically or cytologically proven adenocarcinoma of the lung and (II) ARDS according to Berlin definition were included. Clinical, biological, radiological and cytological features of P-ADC were collected to identify diagnostic clues. Multivariate logistic regression analyses were performed to assess factors associated with ICU and hospital mortality.ResultsAmong the 24 patients included [70 (61–75) years old, 17 (71%) males], the cancer diagnosis was performed during the ICU stay in 19 (79%), and 17 (71%) required mechanical ventilation. The time between the first symptoms and the diagnosis of P-ADC was 210 days (92–246 days). A non-resolving pneumonia after 2 (2 to 3) antibiotics lines observed in 23 (96%) patients with a 34 mg/L (19 to 75 mg/L) plasma C-reactive protein level at ICU admission. Progressive dyspnea, bronchorrhea, salty expectoration, fissural bulging and compressed bronchi and vessels were present in 100%, 83%, 69%, 57% and 43% of cases. Cytological examination of sputum or broncho-alveolar lavage provided a 75% diagnostic yield. The ICU and hospital mortality rates were 25% and 63%, respectively. The time (in days) between first symptoms and diagnosis [odds ratio (OR) 1.02, 95% confidence interval (95% CI): 1.00–1.03, P=0.046] and the Simplified Acute Physiology Score II (OR 1.16, 95% CI: 1.01–1.33, P=0.040) were independently associated with ICU mortality.ConclusionsNon-resolving pneumonia after several antibiotics lines without inflammatory syndrome, associated with progressive dyspnea, salty bronchorrhea, and lobar swelling (i.e., fissural bulging, compressed bronchi and vessels) were suggestive of P-ADC. Delayed diagnosis of diffuse P-ADC seemed an independent prognostic predictor and disease timely recognition may contribute to prognosis improvement.     

HRAS-related epidermal nevus syndromes: Expansion of the spectrum with first branchial arch defects

Epidermal nevus syndrome (ENS) comprises a heterogeneous group of neurocutaneous syndromes associated with the presence of epidermal nevi and variable extracutaneous manifestations. Postzygotic activating HRAS pathogenic variants were previously identified in nevus sebaceous (NS), keratinocytic epidermal nevus (KEN), and different ENS, including Schimmelpenning–Feuerstein–Mims and cutaneous-skeletal-hypophosphatasia syndrome (CSHS). Skeletal involvement in HRAS-related ENS ranges from localized bone dysplasia in association with KEN to fractures and limb deformities in CSHS. We describe the first association of HRAS-related ENS and auricular atresia, thereby expanding the disease spectrum with first branchial arch defects if affected by the mosaic variant. In addition, this report illustrates the first concurrent presence of verrucous EN, NS, and nevus comedonicus (NC), indicating the possibility of mosaic HRAS variation as an underlying cause of NC. Overall, this report extends the pleiotropy of conditions associated with mosaic pathogenic variants in HRAS affecting ectodermal and mesodermal progenitor cells.     

Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment

Background

Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited.

Design

This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols.

Results

Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0–13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p = .0278) and low INHB serum levels (p = .0130) were recorded after CT-HSCT, especially after myeloablative conditioning.

Conclusion

The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.     

Digital optimization of teeth setup in an edentulous patient with partial glossectomy: A case report

The purpose of this clinical report was to describe the use of a piezographic impression associated with computer-aided design and computer-aided manufacturing (CAD–CAM) for teeth setup and of digital tools for neuro-musculo–kinetic analyses. An edentulous patient with hemiglossectomy and heavily resorbed mandible consulted for complete denture rehabilitation to improve their masticatory function and speech. Master casts, wax rims, and piezographic impression were scanned for digital prosthetic work. Two digital try-ins were performed to respect the neutral zone: try-in 1 with posterior crossbite and try-in 2 without crossbite. Muscle activity and mandibular kinetics were performed for each try-in following the MAC2 protocol (six criteria): muscular tone, contraction synchrony, contraction efficiency, interocclusal rest distance, amplitude of mandibular movement, and velocity. Try-in 2 showed better data than try-in 1 in all criteria: muscle tone (respectively 71% vs. 59%), contraction synchrony (79% vs. 75%), contraction efficiency (85% vs. 77%), an increase in range of motion of 3.3 mm, and a better velocity (0.35 ± 0.12 s vs. 0.57 ± 0.14 s, p = 0.008). The piezographic impression, in combination with CAD–CAM, allowed the comparison of two prosthetic designs and the selection of the try-in with the best neuro-musculo–kinetic results.     

Edaravone and mitochondrial transfer as potential therapeutics for vanishing white matter disease astrocyte dysfunction

Introduction

Previous research has suggested that vanishing white matter disease (VWMD) astrocytes fail to fully differentiate and respond differently to cellular stresses compared to healthy astrocytes. However, few studies have investigated potential VWMD therapeutics in monoculture patient-derived cell-based models.

Methods

To investigate the impact of alterations in astrocyte expression and function in VWMD, astrocytes were differentiated from patient and control induced pluripotent stem cells and analyzed by proteomics, pathway analysis, and functional assays, in the absence and presence of stressors or potential therapeutics.

Results

Vanishing white matter disease astrocytes demonstrated significantly reduced expression of astrocyte markers and markers of inflammatory activation or cellular stress relative to control astrocytes. These alterations were identified both in the presence and absence of polyinosinic:polycytidylic acid stimuli, which is used to simulate viral infections. Pathway analysis highlighted differential signaling in multiple pathways in VWMD astrocytes, including eukaryotic initiation factor 2 (EIF2) signaling, oxidative stress, oxidative phosphorylation (OXPHOS), mitochondrial function, the unfolded protein response (UPR), phagosome regulation, autophagy, ER stress, tricarboxylic acid cycle (TCA) cycle, glycolysis, tRNA signaling, and senescence pathways. Since oxidative stress and mitochondrial function were two of the key pathways affected, we investigated whether two independent therapeutic strategies could ameliorate astrocyte dysfunction: edaravone treatment and mitochondrial transfer. Edaravone treatment reduced differential VWMD protein expression of the UPR, phagosome regulation, ubiquitination, autophagy, ER stress, senescence, and TCA cycle pathways. Meanwhile, mitochondrial transfer decreased VWMD differential expression of the UPR, glycolysis, calcium transport, phagosome formation, and ER stress pathways, while further modulating EIF2 signaling, tRNA signaling, TCA cycle, and OXPHOS pathways. Mitochondrial transfer also increased the gene and protein expression of the astrocyte marker, glial fibrillary acidic protein (GFAP) in VWMD astrocytes.

Conclusion

This study provides further insight into the etiology of VWMD astrocytic failure and suggests edaravone and mitochondrial transfer as potential candidate VWMD therapeutics that can ameliorate disease pathways in astrocytes related to oxidative stress, mitochondrial dysfunction, and proteostasis.     

The epidemiology and management of odontomas: a European multicenter study

Oral and Maxillofacial Surgery - Odontoma is the most commonly diagnosed odontogenic tumor of the oral cavity. The objective of the present study was to assess the demographic variables, patterns,...