Response to Liposomal Doxorubicin and Clinical Outcome of HIV-1–Infected Patients with Kaposi’s Sarcoma Receiving Highly Active Antiretroviral Therapy

Abstract

Purpose: HIV-associated Kaposi’s sarcoma (KS) may not resolve despite highly active antiretroviral therapy (HAART). Moreover, the therapeutic goal has shifted from palliative care to long-term durable complete remission. The objective of the study was to assess the impact of liposomal doxorubicin in the treatment of HIV-associated KS in the HAART era. Method: In this prospective, noncomparative, multicenter study, patients with more than 10 cutaneous lesions or visceral disease were treated with 20 mg/m² of liposomal doxorubicin (Caelyx^®) every 3 weeks in addition to their antiretroviral therapy. In addition to tumor measurements and laboratory tests, human herpes virus 8 (HHV-8) polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC) was performed. Results: Out of 79 participants enrolled in the study, 47 (59%) had stage T₁ , 41 (52%) I₁ , and 32 (40%) S₁ . Nine individuals were not evaluable for response, 32 (40%) had complete response, 30 (38%) partial response, 5 (6%) stable disease, and 3 (4%) progression. Regression analysis did not find any statistically significant factor predicting response. HHV-8 PCR was positive in 37/53 (70%) patients with available PBMC samples, and HHV-8 viremia cleared in 14/27 (52%) without correlation with clinical response. Eleven (14%) participants experienced a relapse of KS, while at the last update of data, 49 (62%) remained stable. The only risk factor for recurrence identified was the follow-up time (odds ratio [OR] 1.21, 95% CI 1.07-1.36; p = .002). Conclusion: The response rate of AIDS-associated KS to liposomal doxorubicin administered with HAART was high, and most often the response was durable. HHV-8 viremia did not correlate well with clinical outcome.     

Effects of an integrated Yoga Program on Self-reported Depression Scores in Breast Cancer Patients Undergoing Conventional Treatment: A Randomized Controlled Trial

Aim:

To compare the effects of yoga program with supportive therapy on self-reported symptoms of depression in breast cancer patients undergoing conventional treatment.

Patients and Methods:

Ninety-eight breast cancer patients with stage II and III disease from a cancer center were randomly assigned to receive yoga (n = 45) and supportive therapy (n = 53) over a 24-week period during which they underwent surgery followed by adjuvant radiotherapy (RT) or chemotherapy (CT) or both. The study stoppage criteria was progressive disease rendering the patient bedridden or any physical musculoskeletal injury resulting from intervention or less than 60% attendance to yoga intervention. Subjects underwent yoga intervention for 60 min daily with control group undergoing supportive therapy during their hospital visits. Beck''s Depression Inventory (BDI) and symptom checklist were assessed at baseline, after surgery, before, during, and after RT and six cycles of CT. We used analysis of covariance (intent-to-treat) to study the effects of intervention on depression scores and Pearson correlation analyses to evaluate the bivariate relationships.

Results:

A total of 69 participants contributed data to the current analysis (yoga, n = 33, and controls, n = 36). There was 29% attrition in this study. The results suggest an overall decrease in self-reported depression with time in both the groups. There was a significant decrease in depression scores in the yoga group as compared to controls following surgery, RT, and CT (P < 0.01). There was a positive correlation (P < 0.001) between depression scores with symptom severity and distress during surgery, RT, and CT.

Conclusion:

The results suggest possible antidepressant effects with yoga intervention in breast cancer patients undergoing conventional treatment.     

Serum Zinc Levels in Cutaneous Disorders

Serum zinc levels were studied in 75 patients of different cutaneous disorders and 24 healthy controls. It was found to be significantly lower in acne vulgaris (71.5 ± 21.5µgm/100ml), leprosy(85.9 ± 26.9µgm/100ml) and psoriasis (93.3 ± 25.9µgm/100ml) as compared to healthy controls (105.3 ± 30.1µgm/100ml). No significant correlation was found in other cutaneous disorders studied i.e. vitiligo and aphthous ulcers where serum zinc levels were found to be 97.3 ± 26.6 µgm/100ml and 105.2 ± 23.5 µgm/100ml respectively.Key Words: Acne vulgaris, Aphthous ulcers, Leprosy, Psoriasis, Vitiligo, Zinc     

Prevalent and Emerging Therapies for Osteoporosis

Osteoporosis and fractures associated with it constitute a real and serious socio-medical problem, which only recently has come to the forefront of social consciousness. With increasing number of exservicemen and their dependents, osteoporosis management has become very important in our setup. Currently available pharmacological therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Oral bisphosphonates are the standard treatment for osteoporosis which are associated with significant gastrointestinal side effects and thus poor patient compliance. Newer regimens, including intravenous (IV) formulations of bisphosphonates, have successfully come in vogue with greater patient compliance and equal or better benefits. The real need in osteoporosis treatment is for additional anabolic drugs. The only currently approved anabolic agent for treating osteoporosis is teriparatide (recombinant human parathyroid hormone 1–34), which stimulates new bone formation. Considerable efforts are being made to develop new, more effective treatment for osteoporosis. These novel drugs under trial include those primarily inhibiting osteoclastic bone resorption (like bisphosphonates) such as inhibitors of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling, cathepsin K inhibitors, c-Src kinase inhibitors, integrin inhibitors, chloride channel inhibitors and the drugs with osteo-anabolic actions such as orally active parathyroid hormone (PTH) analogues, calcium sensing receptor antagonists, PTH-related peptide analogues and agents that induce osteoblast anabolism via pathways involving key, recently identified, molecular targets (wnt low-density lipoprotein receptor-related protein-5 signalling; sclerostin antibodies).Key Words: Osteoporosis, Prevalent, Emerging therapies     

Pompe's Disease in Childhood: A Metabolic Myopathy

Background

Myopathy of metabolic origin in childhood occurs due to a variety of conditions. Pompe''s Disease also known as Glycogen storage disease Type II, is a rare storage disorder with clinical presentation akin to spinal muscular atrophy.

Methods

A series of patients with suspected metabolic myopathy were reviewed at a tertiary care service hospital over a period of three years. The diagnosis was confirmed by estimation of acid alpha glucosidase activity.

Result

At our centre, these cases presented with generalized hypotonia, organomegaly (hepatomegaly, cardiomegaly) and congestive cardiac failure. Infantile onset, the most severe form of Pompe''s disease, was the commonest form accounting for 75% of the cases. Four of the babies with infantile onset Pompe''s disease expired, three due to refractory heart failure and one to fulminant respiratory infection before 15 months of age.

Conclusion

Pompe''s Disease is now being increasingly diagnosed, due to definitive enzyme estimation facilities. With the recent availability of enzyme replacement therapy with Myozyme, the prognosis is likely to change for the better.Key Words: Metabolic myopathy, Pompe''s disease, Hypotonia, Cardiomegaly, Hepatomegaly, Acid alpha-glucosidase