Correlation of the Geriatric Assessment with Overall Survival in Older Patients with Cancer.

AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS: This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS: Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION: The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.

Mouse and human Notch-1 regulate mucosal immune responses.

The Notch-1 signaling pathway is responsible for homeostatic tight junction expression in vitro, and promotes barrier function in vivo in the RAG1-adoptive transfer model of colitis. In this study, we sought to determine the role of colonic Notch-1 in the lymphoepithelial crosstalk in health and disease. We utilized in vivo and in vitro knockdown to target the expression of Notch-1. We identified that epithelial Notch-1 is required for appropriate activation of intestinal epithelial cells at steady state and upon inflammatory stimulus. Notch-1 expression modulates mucosal chemokine and cytokine secretion, and FoxP3 and effector T-cell responses. We showed that epithelial Notch-1 controls the immune function of the epithelium through crosstalk with the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathways that, in turn, elicits T-cell responses. Overall, epithelial Notch-1 bridges innate and adaptive immunity in the gut. Our findings highlight an indispensable role for Notch-1-mediated signaling in the intricate epithelial-immune crosstalk, and validate that epithelial Notch-1 is necessary and sufficient to support protective epithelial proinflammatory responses.

Mandibular third molar and inferior alveolar canal.

PURPOSE: The purpose of this study was to determine the incidence of Inferior Alveolar Nerve (IAN) damage after surgical removal of lower third molars, to identify the cause and to construct a predictive model to assess the risk of IAN injury. MATERIALS AND METHODS: Patients were selected from the out patient department after proper clinical and radiological evaluation of mandibular third molars. 50 mandibular third molars of 50 different patients were removed under local anaesthesia. Standardized data collection including the patient's name, age, gender, proximity of inferior alveolar nerve were recorded. RESULTS: A total 6% of the operated sides demonstrated impairment of labial sensation and vast majority of these disturbances subsided completely within six weeks. CONCLUSION: For IAN we found Patient's age, the development of roots, the degree of impaction and the radiographic position of the nerve canal to be significantly correlated to sensory deficit.

Total hip replacement after intra-articular injection of local anaesthetic and steroid.

Intra-articular injections of steroid into the hip are used for a variety of reasons in current orthopaedic practice. Recently their safety prior to ipsilateral total hip replacement has been called into question owing to concerns about deep joint infection. We undertook a retrospective analysis of all patients who had undergone local anaesthetic and steroid injections followed by ipsilateral total hip replacement over a five-year period. Members of the surgical team, using a lateral approach to the hip, performed all the injections in the operating theatre using a strict aseptic technique. The mean time between injection and total hip replacement was 18 months (4 to 50). The mean follow-up after hip replacement was 25.8 months (9 to 78), during which time no case of deep joint sepsis was found. In our series, ipsilateral local anaesthetic and steroid injections have not conferred an increased risk of infection in total hip replacement. We believe that the practice of intra-articular local anaesthetic and steroid injections to the hip followed by total hip replacement is safer than previously reported.

A cysteine protease of Dieffenbachia maculata.

Plants of the genus Dieffenbachia, very popular as indoor ornamental plants, are known for their toxic as well as therapeutic properties. Their toxic manifestations have been partly attributed to their proteolytic activity. The work described in the present paper shows that stem leaves and petiole of Dieffenbachia maculata Schott, a commonly grown species, contain significant proteolytic activity, different parts showing different types of protease activities. Stem showed the highest enzyme activity and this protease was purified about 55 fold by solvent precipitation, gel filtration and ion exchange chromatography. The enzyme has a relative molecular mass of 61 kDa as determined by SDS-PAGE and has an optimum pH of 8.0 and optimum temperature of 50 degrees C. Effects of various substrates, inhibitors and activators indicate that the enzyme is a cysteine protease with leucylpeptidase activity.

Role of platelets in diabetic microangiopathy--an additional factor.

A study of platelet aggregation in 324 diabetes mellitus (DM) patients and 24 patients with microvascular complications of DM (retinopathy) is reported. Platelet aggregation tests showed that DM patients can be divided into two groups: "normal" and "prone." The mean reading and standard deviation (SD) of the normal group was found to be 22.6% (SD 6.99%). The mean reading and standard deviation of the prone group was found to be 60.5% (SD 12.7%) respectively. All patients with microangiopathy had a significant increase, all of them being in the prone range, with a mean of 69.5% (SD 7.2%). Platelet hyperfunction appears to be a high-risk factor for the development of diabetic microangiopathies. A hypothesis postulating platelet hyperfunction as an additional factor along with altered glycoprotein metabolism and explaining the chain of events in the genesis of diabetic microangiopathies is presented.

Clinical laboratory assessment of atherosclerosis--role of hyperlipidaemia and hyperactive platelets.

Hyperlipidaemia and platelet hyperfunction have been considered as high-risk factors for atherogenesis. Simultaneous study of these two parameters was undertaken in 43 patients with atherosclerosis (as evidenced by frank myocardial infarction, MI, in 23 patients and ischemic heart disease, IHD, in 20 patients); and in 36 normal subjects who were matched for age (45 to 60 years). Incidence of either of these parameters being high was 36% in normals, 85% in atherosclerosis. Four subjects with circulating platelet aggregates and hyperlipidaemia showed progression of the lesion by crossing over the category of normal to IHD (two) and from IHD to MI (two). These two risk factors, together or independently, appear to cause and control the progress of atherosclerosis and their simultaneous study can be used for its diagnosis. A concept of subintimal hyperlipidosis is presented since none of the existing theories can explain the existence of atherosclerotic lesions exclusively on the developed vascular musculature.

A new aspect of platelet aggregation and a test to measure it.

Blood platelets which aggregate either in vivo or during collection of samples are not taken into account when aggregation is measured on platelet-rich-plasma (PRP). A new test is presented to measure aggregation in whole blood without ignoring these hyperactive platelets. It is based upon the principles that aggregation is arrested when a smear is prepared and that free and aggregated platelets can be counted differentially on smears. The test was carried out on normal individuals, diabetics, patients of myocardial infarction, women on contraceptives, and also on patients of uremia and Glanzmann's disease. It was compared with the tests of Wu and Hoak, Holdrinet and co-workers, and Born. The reproducibility of the parameters measured by this test is better than those measured by the other tests. The test appears to measure a new dimension of platelet aggregation.

Binding of ethidium bromide and quinacrine hydrochloride to nucleic acids and reconstituted nucleohistones.

Studies of binding of ethidium bromide and quinacrine hydrochloride to native DNA at low ionic strength indicate that for both compounds the binding is selective, with about one binding site for about four nucleotides. Annealing of unfractionated histones to DNA by a salt-gradient dialysis method slightly decreases the binding of the dyes to DNA. Similar observations made with reconstituted preparations by using individual histone fractions reveal that the arginine-rich histones (histones H3 and H4) are most effective in decreasing the binding. The binding studies with ethidium bromide at high ionic strength and with denatured DNA show that strong dye binding to DNA is strongly dependent on the ionic strength and on the secondary structure of DNA. The histones are not effective in decreasing the dye binding under conditions of high ionic strength. The results are consistent with the observations [Oliver & Chalkley (1974) Biochemistry13, 5093-5098; Axel, Melchoir, Sollner-Web & Felsenfield (1974) Proc. Natl. Acad. Sci. U.S.A.71, 4101-4105] that histones form some kind of surface structures on DNA through non-specific interactions and [Kornberg & Thomas (1974) Science184, 865-868; Kornberg (1974) Science184, 868-871; D'Anna & Isenberg (1974) Biochemistry13, 4992-4997; Vandegrift, Serra, Marve & Wagner (1974) Biochemistry13, 5087-5092] that the tendency of arginine-rich histones to aggregate may be an important factor in determining the structure of chromatin.