The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty.

BACKGROUND: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 ("mild") or 6 ("moderate"), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

Epidemiology of basal cell carcinoma: scholarly review.

Basal cell carcinoma (BCC) is the most common cancer in white-skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation (UVR) related skin cancers (i.e. field cancerization). As a result, the disability-adjusted life years and healthcare costs have risen significantly in recent decades. BCC is a complex disease, in which the interplay between UVR, phenotype (UVR-sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis. Prevention programmes with continual refinements and improvements could be of major importance in tackling the growing skin cancer problem. To provide the most appropriate BCC care, physicians should engage in shared decision-making and choose their treatments wisely.

Chemotherapy and quality of life: a case study.

The deteriorating effects of chemotherapy on cancer patients are well documented, so is the need and impact of psychological, behavioural, or educative interventions in improving quality of life. In the developing countries, cancer centres have a very high patient load and providing quality treatment and achieving good survival is still the first priority. However, in the pursuit of quality of survival, the quality of life is often ignored. Psychological and/or behavioural interventions that could enable the patient to cope better, be independent and well informed about the treatment which might improve quality of life of remaining years. This report discusses a case of a 46-year-old female breast cancer patient and her views on the impact of chemotherapy on her life.

Higher distress relates to poor quality of life in patients with head and neck cancer.

Cancers of the head and neck are unique because they may interfere with speech, swallowing, breathing and taste. This study investigated the effect of distress on quality of life in patients with head and neck cancer undergoing treatment and looked at the predictors of distress. 123 patients with head and neck cancer undergoing multimodal treatment were interviewed using the distress inventory for cancer version 2 (DIC2) and the functional assessment of cancer treatment Head Neck (FACT-HN) questionnaire. Nearly half of the patients had early, node negative (N0) disease. The mean distress score was 24.6 and the mean FACT-HN score was 114.5. There was a negative correlation between distress and quality of life scores (patients with higher distress had poor quality of life). Neither surgery nor chemotherapy affected distress or quality of life. Multivariate analysis identified education, occupation, tumor and nodal stage as predictors of distress. Tumor and nodal status influenced overall quality of life. High amounts of distress lead to poor quality of life in patients with head and neck cancers. Financial security, understanding and support from the partner reduced distress in these patients.

Distress overlaps with anxiety and depression in patients with head and neck cancer.

Psychological problems in cancer patients often go unrecognized until they are specifically sought. This is more in patients with depression as they are reluctant to complain about their symptoms. The present study was carried out to evaluate the relation of distress with anxiety and depression in 123 patients with head and neck cancers using Distress Inventory for Cancer version 2 (DIC2) and the Hospital Anxiety and Depression scale (HADS). The mean DIC 2 scores were 24.6 while that of subscales ranged from 2.6 to 11.0. Fifteen patients were found to have clinical caseness for anxiety while 12 (10%) were caseness for depression. Total distress, emotional and social distress subscales were found to have positive correlation with anxiety and depression suggesting a possible overlap of two constructs. In multivariate analysis only belief in god was found to significantly affect the distress. Results of present study suggest significant psychological morbidity in head neck cancer patients undergoing curative treatment. This is the first study reporting on the psychometric properties of distress inventory on cancer version 2 since its validation, the results suggest a possible overlap of two constructs similar to that seen with other tools on distress and this may have major implications for clinical practice.

FACT-G: reliability and validity of the Malayalam translation.

BACKGROUND: Emphasis is currently being placed on the need for quality of life in cancer survivors. There is a great need to identify an appropriate tool for quality of life estimation in these linguistically and culturally different settings. PATIENTS AND METHOD: The Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire was translated into the Malayalam language complying with the standard cross-cultural translation methodology. The tool was validated and used for estimating quality of life (QOL) of 214 cancer patients undergoing treatment with curative intent. RESULTS: Cronbach's alpha for the Malayalam version of the FACT-G was 0.8, and for the subscales it ranged from 0.64 to 0.83, compared to source tool alpha of 0.89, with the subscale's ranging from 0.63 to 0.89. The mean overall FACT-G score was 79.8 (standard deviation [SD] = 18.7). Socio-economic factors such as education, education of the spouse, occupation of the spouse, and family income were found to influence FACT-G scores. CONCLUSION: Despite cultural variations, the local Malayalam language version of the FACT-G scale was found to be reliable like the source scale and sensitive cross-culturally. The instrument makes it possible to identify domains influencing QOL and thereby may help direct interventions to them.

Central Mucoepidermoid carcinoma of mandible - A case report and review of the literature.

BACKGROUND: Primary central mucoepidermoid carcinoma of jaws is a rare lesion comprising 2-3% of all mucoepidermoid carcinomas reported in literature. CASE PRESENTATION: The case presented here illustrates the hypothesis that its specific pathogenesis is unknown. CONCLUSIONS: Mucoepidermoid carcinoma of the jaw is a rare tumour of unknown aetiology. Although about a 100 cases has been reported in literature, the speculation on its aetiopathogenesis has mainly centred on the pluripotential capabilities of the epithelial lining of odontogenic cysts.

Oral cancer in Southern India: the influence of body size, diet, infections and sexual practices.

Between 1996 and 1999, we carried out a study in Southern India on risk factors for oral cancer. The study included 591 incident cases of cancer of the oral cavity (282 women) and 582 hospital controls (290 women). Height was unrelated to oral cancer risk. Body mass index (weight in kilograms/height in metres squared) was inversely associated with risk (P for trend<0.001). Paan chewers with low BMI were at particularly high risk. Risk was increased among subjects consuming meat (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.00-2.37), ham and salami (OR 4.40, 95% CI 2.88-6.71) two or more times per week. Frequent consumption of fish, eggs, raw green vegetables, cruciferous vegetables, carrots, pulses, apples or pears, citrus fruit, and overall consumption of vegetables and fruit decreased oral cancer risk (P for trend for each of these items less than or equal to 0.001). The risk associated with low consumption of vegetables was higher among smokers than among non-smokers. Men, but not women, who practised oral sex had an increased oral cancer risk (OR 3.14, 95% CI 1.15-8.63). Women with more than one sexual partner during life were at increased oral cancer risk (OR 9.93, 95% CI 1.57-62.9).

Salvage chemotherapy and surgery for radio recurrent carcinoma glottis.

Chemoradiotherapy is increasingly used in advanced laryngeal cancers. Failures are generally managed by surgery. They include histologically confirmed recurrent or residual disease or a symptomatic life threatening treatment sequelae. Tumour recurrence or residivism can be managed by chemotherapy when radical surgery is either refused by the patient or if the general condition of the patient do not permit it. However surgery becomes inevitable when life threatening treatment sequelae like absolute pharyngo-oesophageal stricture and aspiration sets in.

Quality of life in breast cancer patients: validation of a FACT-B Malayalam version.

BACKGROUND: Recent advances in diagnosis and treatment of cancer have led to an increase in cancer survival, and hence, there is a greater emphasis on quality beside quantity of survival. Developing countries too have begun to recognize the need for monitoring quality of life (QOL). However, in most of the developing countries, a validated and reliable tool for the purpose is yet to be realized. MATERIAL AND METHOD: The functional assessment of chronic illness therapy (FACIT) system is a collection of QOL questionnaires targeted to measure QOL in chronic illness. The functional assessment of cancer therapy for breast cancer (FACT-B) was translated into the local language (Malayalam) and tested for validity and reliability. RESULTS: The tool thus developed showed substantial sensitivity, as does the source tool. The Cronbach's alpha for the total FACT-B was 0.87, which is similar to the alpha of 0.9 observed in the FACT-B English version. The mean FACT-B score was 94.3 compared to 112.8 for the source tool. CONCLUSION: The Malayalam translation of the FACT-B questionnaire was developed, tested and validated, and was found satisfactory in comparison to the source tool.

Psychological distress in cancer patients: hypothesis of a distress model.

A substantial body of research suggests links between stress, coping and cancer. Research also implicates the immune system as a link between stressful events and cancer. The current trend in research in the area of psycho-oncology attempts to define the types of stress and coping mechanisms being used in order to identify predictors of psychological distress. Based on the available review of literature, the impact of distress does seem to play a prominent role in the transition from a state of health to that of ill-health or even a terminal event. In the light of these studies, a distress model for the cancer patient has been hypothesized here.

Primary tuberculosis of the tongue: report of three cases.

Tuberculosis of the oral cavity is uncommon and poses a diagnostic challenge. We report three patients with primary tuberculosis of the tongue, all of whom responded well to treatment and were cured.

Primary malignant chest wall tumours.

Neoplasms of the chest wall are not uncommon. Majority of the tumours occurring in the chest wall are benign. The tumours may arise from the soft tissues,connective tissues or bone. Metastatic tumours can arise as a result of direct infiltration or haematogenous spread. The management of these tumours is challenging. Resection of the chest wall with or without the excision of ribs, require reconstruction not only for aesthetic reasons but also for providing the stability to the chest wall which is of prime importance in maintaining the respiratory functions. In this article, 46 cases of the primary malignant chest wall tumours seen over a period of 5 years are reviewed.