Reduced alpha diversity of the oral microbiome correlates with short progression-free survival in patients with relapsed/refractory multiple myeloma treated with ixazomib-based therapy (AGMT MM 1, phase II trial).

Alterations in the human microbiome have been linked to several malignant diseases. Here, we investigated the oral microbiome of 79 patients with relapsed/refractory multiple myeloma (MM) treated with ixazomib-thalidomide-dexamethasone. Increased alpha diversity (Shannon index) at the phylum level was associated with longer progression-free survival (PFS) (10.2 vs 8.5 months, P = .04), particularly in patients with very long (>75% quartile) PFS . Additionally, alpha diversity was lower in patients with progressive disease (P < .05). These findings suggest an interrelationship between the oral microbiome and outcome in patients with MM and encourage a novel direction for diagnostic and/or therapeutic strategies.

Quality of life in patients with relapsed/refractory multiple myeloma during ixazomib-thalidomide-dexamethasone induction and ixazomib maintenance therapy and comparison to the general population.

This trial evaluated quality of life (QoL) using the EORTC QLQ-C30 and the EORTC QLQ-MY20 instruments in 90 patients with relapsed/refractory multiple myeloma during induction and maintenance therapy with eight cycles of ixazomib-thalidomide-dexamethasone, followed by 12 months of ixazomib maintenance therapy. When patient's baseline QoL was compared with data of the general population, a significant impairment in health-related QoL, physical, role, and social functioning and several other dimensions, as well as more pain and fatigue, was noted. Induction therapy resulted in significant improvement of pain and worsening of neuropathy, with no significant variation of other parameters. During maintenance treatment, scores for most dimensions including health-related QoL, physical functioning and pain, improved, while for neuropathy no improvement was observed. Time to deterioration (≥10 score points) of health-related QoL, physical functioning, pain, and neuropathy was distinctly shorter than time to progression. Health-related QoL and physical functioning at baseline correlated with overall survival.

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma.

BACKGROUND: Ixazomib-revlimid-dexamethason showed significant activity in relapsed/refractory multiple myeloma (RRMM). Here, we evaluate ixazomib in combination with thalidomide and dexamethasone for induction treatment followed by ixazomib maintenance therapy in RRMM patients. METHODS: Ninety patients have been included. Ixazomib-thalidomide-dexamethasone (4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly) was scheduled for eight cycles followed by maintenance with ixazomib for one year. RESULTS: The overall response rate was 51.1%, 23.3% achieved CR or VGPR and 10% MR resulting in a clinical benefit rate of 61.1%. In patients completing ≥2 cycles, the rates were 60.5%, 27.6% and 68.4%, respectively. Median progression-free survival (PFS) was 8.5 months in all, and 9.4 months in those completing ≥2 cycles. Response rates, PFS and overall survival (OS) were similar in patients with and without t(4;14) and/or del(17p), but PFS and OS was significantly shorter in patients with gain of 1q21. Multivariate regression analysis revealed gain of 1q21 as the most important factor associated with OS. Ixazomib maintenance resulted in an upgrade in the depth of response in 12.4% of patients. Grade 3/4 toxicities were relatively rare. CONCLUSIONS: Ixazomib-thalidomide-dexamethasone followed by ixazomib maintenance therapy is active and well tolerated in patients with RRMM. TRIAL REGISTRATION NUMBER: NCT02410694.

Health Risks and Interventions in Exertional Heat Stress.

BACKGROUND: With climate change, heat waves are expected to become more frequent in the near future. Already, on average more than 25 000 "heat deaths" are estimated to occur in Europe every year. However, heat stress and heat illnesses arise not just when ambient temperatures are high. Physical exertion increases heat production within the organism many times over; if not enough heat is lost, there is a risk of exertional heat stress. This review article discusses contributing factors, at-risk groups, and the diagnosis and treatment of heat illnesses. METHODS: A selective literature search was carried out on PubMed. Current guidelines and expert recommendations were also included. RESULTS: Apart from muscular heat production (>70% of converted energy), there are other factors that singly or in combination can give rise to heat stress: clothing, climate/acclimatization, and individual factors. Through its insulating properties, clothing reduces the evaporation of sweat (the most effective physiological cooling mechanism). A sudden heat wave, or changing the climate zone (as with air travel), increases the risk of a heat-related health event. Overweight, low fitness level, acute infections, illness, dehydration, and other factors also reduce heat tolerance. In addition to children, older people are particularly at risk because of their reduced physiological adaptability, (multi-)morbidity, and intake of prescription drugs. A heat illness can progress suddenly to life-threatening heat stroke. Successful treatment depends on rapid diagnosis and cooling the body down as quickly as possible. The aim is to reduce core body temperature to <40 °C within 30 minutes. CONCLUSION: Immediately effective cooling interventions are the only causal treatment for heat stroke. Time once lost cannot be made up. Prevention (acclimatization, reduced exposure, etc.) and terminating the heat stress in good time (e.g., stopping work) are better than any cure.

Minimally invasive prosthetic restoration of posterior tooth loss with resin-bonded, wing-retained, and inlay-retained fixed dental prostheses fabricated from monolithic zirconia: A clinical report of two patients.

The esthetics and biocompatibility of ceramic resin-bonded fixed dental prostheses (RBFDPs) are regarded as better than those of their metal ceramic counterparts. However, a high incidence of complications in the posterior arches of ceramic RBFDPs initiated a process of continuous and evolving design development. This clinical report describes 2 successful restorations of a missing posterior tooth with monolithic zirconia RBFDPs with 2 different retainer designs: retentively prepared adhesive wings and inlays.

Fracture load of tooth-implant-retained zirconia ceramic fixed dental prostheses: effect of span length and preparation design.

OBJECTIVES: Evaluation of the effect of different span length and preparation designs on the fracture load of tooth-implant-supported fixed dental prostheses (TIFDPs) manufactured from yttrium-stabilized zirconia frameworks. MATERIAL AND METHODS: Forty-eight TIFDPs were manufactured using a CAD/CAM system and veneered with a press ceramic. Rigidly mounted implants (SLA, diameter 4.1 mm, length 10 mm) in the molar region with a titanium abutment were embedded in PMMA bases pairwise with premolars. All premolars were covered with heat-shrink tubing to simulate physiological tooth mobility. Six different test groups were prepared (a) differing in the preparation design of the premolar (inlay [i]; crown [c]), (b) the material of the premolar (metal [m]; natural human [h]) and (c) the length of the TIFDPs (3-unit [3]; 4-unit [4]). All TIFDPs underwent thermomechanical loading (TCML) (10,000 × 6.5°/60°; 6 × 10(5) × 50 N). The load to fracture (N) was measured and fracture sites were evaluated macroscopically. RESULTS: None of the restorations failed during TCML. The mean fracture loads (standard deviations) were 1,522 N (249) for the 3-unit, inlay-retained TIFDPs on a metal abutment tooth (3-im), 1,910 N (165) for the 3-cm group, 1,049 N (183) for group 4-im, 1,274 N (282) for group 4-cm, 1,229 N (174) for group 4-ih and 911 N (205) for group 4-ch. Initial damages within the veneering ceramic occurred before the final failure of the restoration. The corresponding loads were 24-52% lower than the fracture load values. CONCLUSIONS: All restorations tested could withstand the mastication forces expected. Fracture-load values for 3- and 4-unit inlay-crown and crown-crown-retained TIFDPs should spur further clinical investigation.

Thermal comfort range of a military cold protection glove: database by thermophysiological simulation.

The thermal insulation properties of a military wet/cold protection glove of the German Bundeswehr were investigated using the thermophysiological simulation device CYBOR with a heated full-scale hand model. The aim of this study was the physiology related and more reliable estimation of a database for the thermal comfort range of the glove in terms of environmental limit temperatures and maximum safe wearing times (limit times). For that purpose the simulation device CYBOR is equipped with a control feature allowing the simulation of the physiological effect that the blood flow into the hands as the dominant heat source is reduced with decreasing skin temperature (vasoconstriction effect). In the simulation test, the criterion defining the thermal comfort range of the glove was the maintenance of a minimum hand phantom skin temperature of 15 degrees C. For various assumed metabolic rates between 50 and 175 W m(-2) and environmental temperatures down to -22 degrees C, the maximum safe wearing times within the thermal comfort range of the military glove were estimated between only 20 min and almost 1 h. The used simulation scenario for the prediction of environmental limit temperatures, however, tends to deliver too low values in correlation to the estimated limit times and needs further critical consideration. The estimated data concerning the thermal comfort range of the wet/cold protection glove of the German Bundeswehr leads to the recommendation for a use of this model in mild cold climatic regions. The presented thermophysiological simulation procedure for the evaluation of the cold protection properties of gloves in terms of maximum safe wearing times within the thermal comfort range can be a useful tool to establish practical operating instructions for soldiers or civilians acting in cold environments.