Hyperfractionated Cyclophosphamide and Dexamethasone Alone or in Combination with Daratumumab and/or Carfilzomib for the Treatment of Relapsed or Refractory Multiple Myeloma: A Single-Center Retrospective Analysis.

BACKGROUND: Hyperfractionated cyclophosphamide and dexamethasone (HyperCd) alone, or with carfilzomib(K) and/or daratumumab(D), represents a potential treatment option when rapid disease control is needed for patients with aggressive presentations of relapsed/refractory multiple myeloma (RRMM). PATIENTS AND METHODS: This is a single-center, retrospective analysis of adult patients with RRMM who received HyperCd with or without K and/or D between May 1, 2016 and August 1, 2019 at the University of Texas MD Anderson Cancer Center. We here report treatment response and safety outcomes. RESULTS: Data from 97 patients, 12 with plasma cell leukemia (PCL), were reviewed in this analysis. Patients had had a median of 5 prior lines of therapy and received a median of 1 consecutive cycle of hyperCd-based therapy. The overall response rate (ORR) of all patients was 71.8% (HyperCd 75%, HyperCdK 64.3%, D-HyperCd 73.3%, and D-HyperCdK 76.9%). Median progression-free survival and overall survival among all patients was 4.3 months (HyperCd 3.1 months, HyperCdK 4.5 months, D-HyperCd 3.3 months, and D-HyperCdK 6 months) and 9.0 months (HyperCd 7.4 months, HyperCdK 9.0 months, D-HyperCd 7.5 months, and D-HyperCdK 15.2 months), respectively. Grade 3/4 hematologic toxicities were common, thrombocytopenia being the most frequent at 76%. Notably, 29-41% of patients per treatment group had existing grade 3/4 cytopenias at initiation of hyperCd-based therapy. CONCLUSION: HyperCd-based regimens provided rapid disease control among MM patients, even when heavily pre-treated and with few remaining treatment options. Grade 3/4 hematologic toxicities were frequent, but manageable with aggressive supportive care.

Stress hyperglycaemia is associated with poor functional outcomes in patients with acute ischaemic stroke after intravenous thrombolysis.

BACKGROUND: Transient hyperglycaemia in the context of illness with or without known diabetes has been termed as 'stress hyperglycaemia'. Stress hyperglycaemia can result in poor functional outcomes in patients with acute ischaemic stroke (AIS) who underwent mechanical thrombectomy. We investigated the association between stress hyperglycaemia and clinical outcomes in AIS patients undergoing intravenous thrombolysis (IVT). METHODS: We examined 666 consecutive patients with AIS who underwent IVT from 2006 to 2018. All patients had a glycated haemoglobin level (HbA1c) and fasting venous blood glucose measured within 24 h of admission. Stress hyperglycaemia ratio (SHR) was defined as the ratio of the fasting glucose to the HbA1c. Univariate and multivariate analyses were employed to identify predictors of poor functional outcomes (modified Rankin Scale 3-6 at 3 months) after IVT. RESULTS: Three-hundred and sixty-one patients (54.2%) had good functional outcomes. These patients tended to be younger (60.7 ± 12.7 vs. 70 ± 14.4 years, P < 0.001), male (70.7% vs. 51.5%, P < 0.001), had lower prevalence of atrial fibrillation (13.0% vs. 20.7%, P = 0.008) and lower SHR (0.88 ± 0.20 vs. 0.99 ± 26, P < 0.001). Patients with high SHR (≥0.97) were slightly older than those with low SHR (<0.97) and were more likely to have diabetes mellitus. On multivariate analysis, higher SHR was independently associated with poor functional outcomes (adjusted odds ratio 3.85, 95% confidence interval 1.59-9.09, P = 0.003). CONCLUSION: SHR appears to be an important predictor of functional outcomes in patients with AIS undergoing IVT. This may have important implications on the role of glycaemic control in the acute management of ischaemic stroke.

Establishing the Maximum Collectivity in Highly Deformed N=Z Nuclei.

The lifetimes of the first excited 2^{+} states in the N=Z nuclei ^{80}Zr, ^{78}Y, and ^{76}Sr have been measured using the γ-ray line shape method following population via nucleon-knockout reactions from intermediate-energy rare-isotope beams. The extracted reduced electromagnetic transition strengths yield new information on where the collectivity is maximized and provide evidence for a significant, and as yet unexplained, odd-odd vs even-even staggering in the observed values. The experimental results are analyzed in the context of state-of-the-art nuclear density-functional model calculations.

Determining the rp-process flow through 56Ni: resonances in 57Cu(p,γ)58Zn identified with GRETINA.

An approach is presented to experimentally constrain previously unreachable (p, γ) reaction rates on nuclei far from stability in the astrophysical rp process. Energies of all critical resonances in the (57)Cu(p,γ)(58)Zn reaction are deduced by populating states in (58)Zn with a (d, n) reaction in inverse kinematics at 75 MeV/u, and detecting γ-ray-recoil coincidences with the state-of-the-art γ-ray tracking array GRETINA and the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The results reduce the uncertainty in the (57)Cu(p,γ) reaction rate by several orders of magnitude. The effective lifetime of (56)Ni, an important waiting point in the rp process in x-ray bursts, can now be determined entirely from experimentally constrained reaction rates.

Evaluation of two chlorhexidine-alcohol-based skin disinfectants in blood donation setting.

BACKGROUND: Source reduction is important in minimizing bacterial-contaminated risk of blood products, but previous evaluation of chlorhexidine (CHX) was confounded by inability of Tween and lecithin to neutralize CHX. The study aims to address this limitation and also evaluates the effectiveness of two CHX­alcohol-based skin disinfectants in blood donation setting. METHODS: A two-stage observational study was conducted. A single step 2% chlorhexidine gluconate/70% isopropyl alcohol brush (CHX/IPA-1) was first compared with current skin disinfection procedure consisting of sequential application of 10% povidone-iodine and 70% isopropyl alcohol (PI/IPA). Standard plates with conventional neutralizers (0·3% Tween-80, 0·1% lecithin) were used to enumerate residual bacterial counts. Then, CHX/IPA-1 was compared with another applicator CHX/IPA-2 with identical disinfectant contents using in-house plates with neutralizers (3% Tween-80, 0·3% lecithin, 0·1% histidine, 0·5% sodium thiosulphate, 3% saponin, 1% ether sulphate) having enhanced ability to neutralize CHX. RESULTS: All three products were found to reduce plate counts by > 2 log10 after disinfection. The CHX/IPA-1 group gave fewer residual bacterial growth on standard plates than PI/IPA group (5·9% vs. 61·7%, P < 0·001). With the use of in-house plates, residual bacterial growth was of no difference in both CHX/IPA-1 and CHX/IPA-2 groups (42·5% vs. 49·4%, P = 0·26). CONCLUSION: Good efficacy was observed with one-stage application of CHX/IPA in predonation skin disinfection and it could replace PI/IPA. However, the efficacy of CHX/IPA could be grossly overestimated in testing with standard plates because of insufficient neutralization

Nuclear structure towards N = 40 60Ca: in-beam γ-ray spectroscopy of 58,60Ti.

Excited states in the neutron-rich N = 38, 36 nuclei (60)Ti and (58)Ti were populated in nucleon-removal reactions from (61)V projectiles at 90 MeV/nucleon. The γ-ray transitions from such states in these Ti isotopes were detected with the advanced γ-ray tracking array GRETINA and were corrected event by event for large Doppler shifts (v/c ∼ 0.4) using the γ-ray interaction points deduced from online signal decomposition. The new data indicate that a steep decrease in quadrupole collectivity occurs when moving from neutron-rich N = 36, 38 Fe and Cr toward the Ti and Ca isotones. In fact, (58,60)Ti provide some of the most neutron-rich benchmarks accessible today for calculations attempting to determine the structure of the potentially doubly magic nucleus (60)Ca.

Evolution of collectivity in 72Kr: evidence for rapid shape transition.

The transition rates from the yrast 2+ and 4+ states in the self-conjugate 72Kr nucleus were studied via lifetime measurements employing the GRETINA array with a novel application of the recoil-distance method. The large collectivity observed for the 4+→2+ transition suggests a prolate character of the excited states. The reduced collectivity previously reported for the 2+→0+ transition was confirmed. The irregular behavior of collectivity points to the occurrence of a rapid oblate-prolate shape transition in 72Kr, providing stringent tests for advanced theories to describe the shape coexistence and its evolution.

Reduction in vasovagal reaction rate in young first-time blood donors by collecting 350 mL rather than 450 mL.

BACKGROUND: There is a paucity of studies on the magnitude of reduction of vasovagal reaction by reduced collection volume. This study was thus conducted to determine the difference in reaction rates between two collection volumes among the young first-time donors who are at particular risk of reaction. STUDY DESIGN AND METHODS: This retrospective study analyzed 38,436 whole blood donations made by young (aged 16 to 18 years) first-time donors. The effect of collection volume on vasovagal reaction was compared among different weight subgroups for both sexes by chi-square test. RESULTS: For females in all weight subgroups and two of the male lower-weight subgroups, the reduction percentages ranged from 35% to 58% (p < 0.05). It was also noted that, among the females, a higher weight was associated with a higher percent reduction in the reaction rate. CONCLUSION: With reduced collection volume, this study detected large and significant reduction in reaction rates among all females, as well as lower-weight males.

Quadrupole collectivity in neutron-rich Fe and Cr isotopes.

Intermediate-energy Coulomb excitation measurements are performed on the N ≥ 40 neutron-rich nuclei (66,68)Fe and (64)Cr. The reduced transition matrix elements providing a direct measure of the quadrupole collectivity B(E2;2(1)(+) → 0(1)(+)) are determined for the first time in (68)Fe(42) and (64)Cr(40) and confirm a previous recoil distance method lifetime measurement in (66)Fe(40). The results are compared to state-of-the-art large-scale shell-model calculations within the full fpgd neutron orbital model space using the Lenzi-Nowacki-Poves-Sieja effective interaction and confirm the results of the calculations that show these nuclei are well deformed.

Low-energy enhancement in the photon strength of 95Mo.

A new experimental technique is presented using proton-γ-γ correlations from (94)Mo(d,p)(95)Mo reactions which allows for the model-independent extraction of the photon strength function at various excitation energies using primary γ-ray decay from the quasicontinuum to individual low-lying levels. Detected particle energies provide the entrance excitation energies into the residual nucleus while γ-ray transitions from low-lying levels specify the discrete states being fed. Results strongly support the existence of the previously reported low-energy enhancement in the photon strength function.

Lifetime measurement of the 2(1)+ state in 20C.

Establishing how and when large N/Z values require modified or new theoretical tools is a major quest in nuclear physics. Here we report the first measurement of the lifetime of the 2(1)+ state in the near-dripline nucleus 20C. The deduced value of τ(2(1)+)=9.8±2.8(stat)(-1.1)(+0.5)(syst) ps gives a reduced transition probability of B(E2; 2(1)+→0(g.s.)+)=7.5(-1.7)(+3.0)(stat)(-0.4)(+1.0)(syst) e2 fm4 in good agreement with a shell model calculation using isospin-dependent effective charges.

New superheavy element isotopes: ²4²Pu(48Ca,5n) ²85114.

The new, neutron-deficient, superheavy element isotope ²85114 was produced in 48Ca irradiations of ²4²Pu targets at a center-of-target beam energy of 256 MeV (E*=50 MeV). The α decay of ²85114was followed by the sequential α decay of four daughter nuclides, 281Cn, 277Ds, 273Hs, and 269Sg. 265Rf was observed to decay by spontaneous fission. The measured α-decay Q values were compared with those from a macroscopic-microscopic nuclear mass model to give insight into superheavy element shell effects. The²4²Pu (48Ca,5n²)²85114 cross section was 0.6(-0.5)+0.9 pb.

Molecular evidence for tick-borne encephalitis virus in ticks in South Korea.

To investigate whether tick-borne encephalitis viruses (TBEVs) are present in South Korea, Korean ixodid ticks were tested for TBEV RNA. Ticks (n = 2460) were collected from wild and domestic animals or by flagging at forest and grassland in 12 regions of five provinces in 2005-06. Four species in two genera were identified, yielding 197 sample pools (1-20 ticks per pool); from these, 12 envelope protein gene fragments of TBEV were amplified by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). Ten of the 2104 adult ticks (0.4%) and two of the 356 nymph ticks (0.2%) were positive for the envelope (E) gene of TBEV. Twelve TBEV RNA-positive samples were detected in Gyeonggi and Gangwon provinces. Phylogenetic analysis showed that the E genes of the TBEV isolates were clustered with the Western European subtype (98% identity). This study suggests that TBEVs may exist in Korea.

Lifetime measurement of the first excited 2+ state in 16C.

The lifetime of the 2_+(1) state in 16C has been measured with the recoil distance method using the 9Be(9Be,2p) fusion-evaporation reaction at a beam energy of 40 MeV. The mean lifetime was measured to be 11.7(20) ps corresponding to a B(E2;2_+(1)-->0+) value of 4.15(73)e_2 fm_4 [1.73(30) W.u.], consistent with other even-even closed shell nuclei. Our result does not support an interpretation for "decoupled" valence neutrons.

Motional narrowing and ergodic bands in excited superdeformed states of 194Hg.

The E(gamma) - E(gamma) coincidence spectra from the electromagnetic decay of excited superdeformed states in (194)Hg reveal surprisingly narrow ridges, parallel to the diagonal. A total of 100-150 excited bands are found to contribute to these ridges, which account for nearly all the unresolved E2 decay strength. Comparison with theory suggests that these excited bands have many components in their wave functions, yet they display remarkable rotational coherence. This phenomenon can be explained in terms of the combination of shell effects and motional narrowing.

Return of collective rotation in 157Er and 158Er at ultrahigh spin.

A new frontier of discrete-line gamma-ray spectroscopy at ultrahigh spin has been opened in the rare-earth nuclei (157,158) Er. Four rotational structures, displaying high moments of inertia, have been identified, which extend up to spin approximately 65 variant Planck's over 2pi and bypass the band-terminating states in these nuclei which occur at approximately 45 variant Planck's over 2pi. Cranked Nilsson-Strutinsky calculations suggest that these structures arise from well-deformed triaxial configurations that lie in a valley of favored shell energy which also includes the triaxial strongly deformed bands in (161-167) Lu.

Helicobacter pylori eradication prior to initiation of long-term non-steroidal anti-inflammatory drug therapy in Chinese patients-a cost-effectiveness analysis.

BACKGROUND: Recent randomized clinical trials suggested that eradication of Helicobacter pylori prior to initiation of non-steroidal anti-inflammatory drug (NSAID) therapy would reduce the rate of peptic ulcer disease (PUD). OBJECTIVE: To analyze the cost-effectiveness of H. pylori eradication prior to initiation of long-term NSAID therapy for prevention of NSAID-induced PUD in a cohort of Chinese patients at high risk for PUD. METHODS: Clinical and economic data of 100 participants from a previously reported clinical trial conducted in Hong Kong were analyzed. Patients with a history of peptic ulcers were randomized to 1-week omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg twice daily (eradication group; n = 51) or 1-week omeprazole 20 mg twice daily (omeprazole group; n = 49) before initiation of diclofenac 100 mg daily for 6 months. The rates of PUD and healthcare utilization for routine follow-up as well as for management of symptomatic PUD of the 2 groups were retrieved from medical records. RESULTS: The rate of symptomatic ulcers in eradication group and omeprazole group were 3.9% and 18%, respectively. The mean direct medical cost of the eradication group was significantly lower than that of the omeprazole group by 30% (US dollar 797 (95% CI = 685 - 909) versus US dollar 1,128 (95% CI = 879 - 1,377)) (p = 0.018). The results were robust to variation of all the cost items. CONCLUSIONS: H. pylori eradication prior to initiation of NSAID therapy appeared to reduce the ulcer rate and mean direct medical cost when compared to no eradication for Chinese H. pylori-infected NSAID users at high risk for PUD.

Sheng mai san, a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke in the rat.

1. There is evidence that the induction of inducible nitric oxide synthase (iNOS) and peroxynitrite by ischaemia/reperfusion may lead to renal cell injury. Herein, we investigated whether Sheng mai san (SMS), a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke by reducing iNOS-dependent nitric oxide (NO) and peroxynitrite formation. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 43 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and renal blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, both colonic temperature and renal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma NO, creatinine and blood urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and peroxynitrite, were significantly higher in heat stroke rats compared with their normothermic controls. 3. Pretreatment with SMS (1.2 g/day per rat for 7 consecutive days before the initiation of heat stress) significantly attenuated the heat stroke-induced arterial hypotension, hyperthermia, renal ischaemia and damage, the increased renal immunoreactivity of iNOS and peroxynitrite and the increased plasma levels of NO, creatinine and BUN. Pretreatment with SMS resulted in a prolongation of survival time in heat stroke. 4. The results of the present study suggest that SMS protects against renal ischaemic damage by reducing iNOS-dependent NO and peroxynitrite production during heat stroke.