Acute myeloid leukemia: current progress and future directions

Progress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various indications in AML. These included several targeted therapies like venetoclax, FLT3 inhibitors, IDH inhibitors, and others. The management of AML is complicated, highlighting the need for expertise in order to deliver optimal therapy and achieve optimal outcomes. The multiple subentities in AML require very different therapies. In this review, we summarize the important pathophysiologies driving AML, review current therapies in standard practice, and address present and future research directions.Subject terms: Prognosis, Health services     

Fine structure of the adrenocortical homologue in the north American eel and modifications following seawater adaptation

The ultrastructure of the adrenocortical homologue (AH) of the north American eel (Anguilla rostrata) was studied from freshwater and long-term (1.5 years) seawater (SW) adpated animals. The AH tissue situated in the wall of cardinal veins is surrounded by a thin layer of collagenous capsule; in the region away from the vein wall, parenchymal cells are separated by interstitial lacunae containing collagen bundles, capillaries, chromaffin cells and nerve fibers often applied closely to the surface of AH cells. The free surface of the cell near the vein wall, capillaries or interstitial space extends numerous slender microplicae. The cytoplasm is characterized by the presence of mitochondria with tubular cristae, a network of smooth endoplasmic reticulum, a few cisternae of rough surfaced endoplasmic reticulum, well developed Golgi apparatus, coated vesicles, centrioles, cilium, filaments, microtubules, dense bodies of variable nature and a scarcity of liposomes. The cell nuclei possess invaginated cytoplasmic pseudo-inclusions. Electron histochemical reaction for free cholesterol revealed the occurrence of needle-shaped crystals mainly associated with surface microplicae and smooth endoplasmic reticulum, which seems to be the major organelle for storage or synthesis of this steroid precursor. SW animals indicated ultrastructural signs of stimulated steroid synthesis and secretion, i.e., high degree of pseudo-follicle formation, increased electron density of mitochondria, greater abundance of lysosomal dense bodies, hyperactivity of Golgi apparatus and dilation of smooth endoplasmic reticulum tubules. Some SW fishes showed extensive deposition of osmiophilic inclusions in the mitochondria and stacks of elongated cup-shaped mitochondria. Chronic seawater acclimation enhances AH activity as judged by ultrastructural criteria with ultimate mitochondrial degeneration resulting possibly from prolonged cortisol hypersecretion; the latter may be linked with physiologic re-adjustment of ionic transfer mechanism in hyperosmotic medium.     

Open Classic Latarjet Procedure Performed Using Freehand Technique—Surgical Technique and Outcome

IntroductionLatarjet procedure is commonly performed for recurrent anterior shoulder instability with glenoid side bone loss. Classic Latarjet procedure can be performed using specially designed drill guides, jigs, or by freehand technique. Here we have described a technical note on classic Latarjet procedure performed with freehand technique utilizing simple rulers and caliper. The functional and radiological outcomes of our patients have also been analysed.Material and Methods149 open classic Latarjet procedures were performed using our technique between March 2015 and July 2018. The mean age of the patients was 32.95 years (Range 22–59 years). The functional outcome of the patients was measured using Western Ontario Shoulder Instability (WOSI) and Oxford Shoulder Instability Score (OSIS) at 2 years of follow-up. Screw and graft positioning were studied in 24 consecutive patients with a postoperative computed tomography (CT) scan.ResultsThere was no incidence of recurrent subluxation or dislocation post-surgery. Mean OSIS score increased from 15.63 ± 3.20 preoperatively to 42.44 ± 3.88 postoperatively (p value < 0.05). WOSI score decreased significantly from 62.54% ± 8.24 to 10.26 ± 6.33 postoperatively at 2-year follow-up (p value < 0.05). Postoperative CT scan also showed satisfactory screw placement in all patients.ConclusionOpen Latarjet procedure performed using freehand technique provides good functional and radiological outcomes in patients with recurrent anterior shoulder instability with glenoid side bone loss.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43465-021-00385-7.     

Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

Autism as a disorder of prediction

A rich collection of empirical findings accumulated over the past three decades attests to the diversity of traits that constitute the autism phenotypes. It is unclear whether subsets of these traits share any underlying causality. This lack of a cohesive conceptualization of the disorder has complicated the search for broadly effective therapies, diagnostic markers, and neural/genetic correlates. In this paper, we describe how theoretical considerations and a review of empirical data lead to the hypothesis that some salient aspects of the autism phenotype may be manifestations of an underlying impairment in predictive abilities. With compromised prediction skills, an individual with autism inhabits a seemingly “magical” world wherein events occur unexpectedly and without cause. Immersion in such a capricious environment can prove overwhelming and compromise one’s ability to effectively interact with it. If validated, this hypothesis has the potential of providing unifying insights into multiple aspects of autism, with attendant benefits for improving diagnosis and therapy.     

Influence of Thread Design on Implant Positioning in Immediate Implant Placement

Background: It is generally believed that implants placed in extraction sockets have a tendency to shift in the facial direction during insertion. The purpose of this study is to investigate the effect of different thread designs on the final implant position in immediate implant placement. Methods: In a split‐mouth design involving 11 cadaver heads, each specimen received two implants, one with a square and one with a V‐shaped thread design, in maxillary incisor extraction sockets. The facio‐lingual locations of the drills and the implant were tracked, and the displacements were compared between the two groups. Results: No statistically significant differences were observed between the square and V‐shaped thread design groups. The mean displacements of the different groups showed a general tendency of the implants to be positioned facially compared with the initial drill trajectory. This tendency was greater for implants with square thread design. Conclusion: There was no significant effect of implant thread design on the positioning of implants in extraction sockets.