A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody.

BACKGROUND: An important unmet need for new treatment options remains for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) previously treated with both platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1) antibody. Retrospective studies suggest that previous treatment with immune checkpoint inhibitor might augment the efficacy of subsequent chemotherapy. Here, we conducted a phase II trial aimed to evaluate the efficacy and safety of paclitaxel plus biweekly cetuximab for patients in this setting. PATIENTS AND METHODS: This was a single-arm, multicenter, phase II trial. Key eligibility criteria were R/M-HNSCC, and previous treatment with both platinum-based chemotherapy and PD-1 antibody. Paclitaxel plus biweekly cetuximab consisted of weekly paclitaxel 100 mg/m2 (days 1, 8, 15) and biweekly cetuximab 500 mg/m2 (days 1, 15) with a cycle of 28 days until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) (Common Terminology Criteria for Adverse Events version 5.0). RESULTS: Between August 2020 and August 2022, 35 patients were enrolled, of whom 33 were assessable for response. ORR was 69.6% (95% confidence interval 51.2% to 84.4%). With a median follow-up period for survivors of 16.6 months, median PFS and OS were 5.5 and 13.3 months, respectively. DCR was 93.7%. Twenty-three patients (65%) experienced grade 3 or 4 AEs, including neutropenia (34%), infection (14%), leukopenia (11%), mucositis (8%), and pneumonitis (8%). Eight patients discontinued study treatment due to treatment-related AEs, and no treatment-related death was observed. CONCLUSIONS: Paclitaxel plus biweekly cetuximab showed highly encouraging efficacy and manageable toxicities in R/M-HNSCC patients previously treated with both platinum-based chemotherapy and PD-1 antibody. This combination therapy warrants further investigation in this setting.

New proposal to revise the classification for squamous cell carcinoma of the external auditory canal and middle ear.

BACKGROUND: The prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades. METHODS: Ninety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T1, T2, T3 and T4 was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated. RESULTS: Among patients with T4 disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T4b) was significantly lower than that of patients without these factors (T4a) (25.5 vs 65.5 per cent, p = 0.049). CONCLUSION: It is proposed that stage T4 be subclassified into T4a and T4b according to the prognostic factors.

An estimation of economic effects of tele-home-care: hospital cost-savings of the elderly.

Tele-home-care (or tele-medicine) is being implemented by the application of multimedia such as CATV and ISDN. In this paper, by focusing on the so-called "social hospitalization of the aged," we carry out an estimation of the extent to which tele-home-care based on multimedia can help in saving the cost of hospitalization of the aged in the future. Estimation consists of the following two parts. First, we estimate the trends of the aged population and their hospital expenses using the regression analysis. Second, we assume that new technology such as multimedia and new medical instruments develop according to a logistic curve. Thus, we estimate the rate of diffusion of CATV and ISDN by logistic curves. Then, by multiplying this number by hospital costs per elderly patient as estimated previously, we have been able to calculate the extent to which hospitalization costs can be saved in the entire economy. Our results indicated that in the year 2050, US$257.3 billion, or nearly 7.4% of total hospitalization costs of the aged could be saved by tele-home-care.

Spirostanols obtained by cyclization of pseudosaponin derivatives and comparison of anti-platelet agglutination activities of spirostanol glycosides.

Naturally occurring saponins 3 and 4 have a normal type F ring and alpha-arranged CH(3)-21 group. Treatments of pseudosaponin peracetates 18 and 19 derived from 3 and 4, respectively, with alcoholic KOH, followed by acidification with acetic acid, gave spirostanols 20 and 22 having iso type F rings as major products. Structural analyses of sapogenins and saponins derived from pseudo derivatives 11, 12, 18 and 19 were performed by comparisons of their 1H-NMR spectral data and the X-ray analytical data of 3-O-p-bromobenzoyl sarsasapogenin 7, 3-O-acetyl diosgenin 13 and saponin 20. The mechanisms of ring-closure reaction of the side chain at C-22 of pseudosapogenins and pseudosaponins were deduced using stereomodels of the spirostanols derived from 11 under various reaction conditions. Inhibitory activities of saponin diglycosides 3, 4, 20, 21 and 25 on human platelet agglutinations induced by ADP and ristocetin were compared.

[Effects on the grieving process of the families of people who use home care stations].

The aim of this study was to clarify the effects on the grieving process of bereaved families, and to investigate what visiting nurses should do to provide support. Twelve cases in which nurses from our station provided home care in 1998 were analyzed with regard to the grieving state of the families, the families' physical conditions, social situations, and support systems. The results showed that the number of carers during the patient's period of illness, the support system, and level of communication with medical providers affected the grieving process. To minimize the load on the grieving family and help them achieve closure at an early stage, it is necessary to begin developing care ability and preparing a support system during the period of home treatment. Sufficient emotional care must also be provided for the family, including education in preparing for death. The families lean heavily on medical staff for this, and building a good relationship is therefore vital.

Accurate frequency control of a mode-locked laser diode by reference-light injection.

Injection locking is employed to narrow the spectrum linewidth of individual modes of an active mode-locked laser diode (ML-LD). The multiple modes of the injection-locked ML-LD lie over 3.0 THz with 25-GHz spacing at 30 dB down; their linewidth and stability, ~25 MHz, are nearly the same as those of the master laser. We also demonstrate the accurate frequency measurement of laser diodes stabilized to molecular (H(13)C (15)N ,(13)C(2)H (2)) absorption lines by use of the injection-locked ML-LD.

[Recovered state of iron in female blood donors--after taking an iron supplement].

An iron supplement was given to female blood donors to prevent iron deficiency after blood donation. The levels of items related to red blood cells and serum ferritin (S-Fer) among 17 iron-takers and 31 non-iron-takers were analyzed continuously. In most of the non-iron-takers, the S-Fer levels did not recover within four weeks after the donation of 200ml or 400ml of blood. In the approximately half of the donors, hemoglobin (Hb) levels did not recover either. However, in 59% of those taking iron supplements three times the amount of iron lost by donation, the levels of Hb and S-Fer recovered within two weeks. In the remaining 41%, the Hb levels recovered within four weeks by taking the iron supplement. Four weeks after blood donation, the incidence of iron deficiency anemia among the non-iron-takers increased from 13% to 23% and the incidence of latent iron deficiency among the non-iron-takers increased from 32% to 42%. However, the incidence of iron deficiency anemia among the iron-takers remained 0% and the incidence of latent iron deficiency among the iron-takers decreased from 12% to 6%.

Inhibitory effect of Mg2+ on the protonophoric activity of palmitic acid.

To discriminate whether fatty acids are uncouplers that cause acceleration of State-4 respiration, associated with a decrease in the protonmotive force, or decouplers that increase respiration without associated decrease in the protonmotive force, we examined the effect of palmitate on functions of rat-liver mitochondria under various conditions. We found that palmitate itself increases State-4 respiration, releases oligomycin-inhibited State-3 respiration, inhibits ATP synthesis and ATP<->Pi exchange reaction, and increases H+ permeability in mitochondrial and model bilayer phospholipid membranes. Thus, palmitate is a classical uncoupler of oxidative phosphorylation. However, these effects were inhibited by Mg2+, due to rapid formation of a stable complex between palmitate and Mg2+.

[Clinical evaluation of finger blood pressure measurement devices for home-use].

We evaluated the accuracy of two types of finger blood pressure (BP) measurement devices for home-use (EW276 H, NATIONAL Ltd. and HEM 804F, OMRON Ltd.) by comparing BP values with upper-arm BP measured with a standard mercury column sphygmomanometer in 28 elderly subjects (13 Hypertensives and 15 normotensives). The correlation coefficient of systolic BP value and that obtained by each method was R2 = 0.5 for EW 276H and R2 = 0.6 for HEM 804F. The higher the systolic BP, the greater was the difference between the upper-arm and finger BP values. The magnitude of the difference between finger and upper-arm values for systolic BP did not correlate with pulse wave velocity. An underestimation of the finger BP device in systolic BP was 23.8 mmHg in hypertensives and 7.6 mmHg in normotensives for the EW 276H, and 15.3 and 3.5 mmHg, respectively for the HEM 804F. This study demonstrated a large difference between the finger BP value measured with the home-use devices and upper-arm BP value measured with a standard mercury sphygmonanometer in elderly hypertensive patients. The difference may be due not only to atherosclerotic change, but also to methodological factors related to finger BP measurement.

Injection locking of a highly coherent and high-power diode laser at 1.5 microm.

Injection locking has been employed to improve the coherence of a high-power diode laser at 1.5 microm. The injected high-power laser emitted in a single mode with a side-mode suppression ratio of larger than 30 dB and an output power of 40 mW. The FM noise of the slave laser was nearly the same as that of the submegahertz-linewidth master laser. We have also demonstrated the coherent addition of the master and the injection-locked slave laser with a residual phase error of deltaø < 0.2 rad.

Deterioration of B cell proliferation correlates with dendritic reticulum cell destruction in germinal centers of an AIDS patient. Case study.

A lymph node from a bisexual Caucasian male infected with human immunodeficiency virus (HIV) and in the persistent generalized lymphadenopathy (PGL) stage was studied. Dendritic reticulum cells (DRCs) were well preserved in over half of the germinal centers (GCs), while in the rest, they showed marked destruction, producing patchy or rather wide DRC-depleted areas. Proliferation-associated antigens, i.e., PC antigen and DNA-polymerase alpha, were demonstrated in nuclei of germinal center B cells in areas where the DRC network was intact, while they were prominently depleted in areas where the DRC network was lost. The p-24 viral core antigen was shown to be localized in DRCs, especially those in the process of degeneration. These results suggest that the DRC in this patient, when infected with HIV, were destroyed, and that the resulting DRC depletion led to the suppression of B cell proliferation in GCs.