10 research outputs found

    Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells

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    Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89 Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8 + T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89 Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies.National Institutes of Health (U.S.) (Grant R01-AI087879-06)National Institutes of Health (U.S.) (Grant DP1-GM106409-03)National Institutes of Health (U.S.) (Grant R01-GM100518-04)National Institutes of Health (U.S.) (Grant P01 CA080111

    Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial

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    Ultraviolet protective properties of branded and unbranded sunglasses available in the Indian market in UV phototherapy chambers

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    Background: Patients receiving phototherapy for various dermatoses are at increased risk of eye damage due to ultraviolet (UV) rays. They are prescribed UV protective sunglasses by dermatologists but their exact protecting effects are not known. Aim: To study the ultraviolet protective properties of branded and unbranded UV protective sunglasses available in the Indian market, in UV phototherapy chambers. Methods: Sixteen different branded and unbranded UV protective sunglasses were collected from two opticians in Mumbai. Baseline irradiance of the UV chamber was calculated by exposing the photosensitive probe of UV photometer in the chamber. Then, the photosensitive probe of the UV photometer was covered with the UV protective glass to be studied and irradiance was noted. Such readings were taken for each of the UV protective sunglasses. The percentage reduction in the UV rays' penetration of different UV protective sunglasses was calculated. Results: Thirteen sunglasses provided > 80% reduction in UVA rays penetration, of which four were branded (out of the four branded studied) and nine were unbranded (out of the 12 unbranded studied). More than 70% reduction in UVB penetration was provided by 12 sunglasses, which included 10 unbranded and two branded sunglasses. Conclusion: All branded sunglasses provided good protection against UVA penetration, but UVB protection provided by both branded and unbranded sunglasses was not satisfactory. A few unbranded sunglasses had poor efficacy for UVA and UVB spectra; one branded glass had poor efficacy for protection against the UVB spectrum. The efficacy of sunglasses used for phototherapy should be assessed before use

    A study of clinicopathologic profile of 15 cases of hypopigmented mycosis fungoides

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    Background: Mycosis fungoides (MF) is cutaneous lymphoma of the T-cell lineage. Hypopigmented MF is a clinical variant of MF, described mainly in Asians. This is a retrospective clinicopathologic analysis of hypopigmented MF at a tertiary care center. Aims: To describe the clinicopathologic profile of hypopigmented MF. Methods: Records of clinicopathologic notes over a 5-year period ranging from January 2005 up to December 2009 were reviewed over a period of 3 months, of which 15 cases were diagnosed with hypopigmented MF based on clinicopathologic correlation. Results: Hypopigmented MF was found to be more common in males, and between second and fourth decades of life. The latent period between onset and diagnosis was around 3.83 years. Most of the patients were asymptomatic 80% (12/15), with skin changes of subtle atrophy in 46.66% (7/15), scaling in 20% (3/15) and focal changes of poikiloderma in 26.66% (4/15) patients. Most common sites of distribution of the lesions were the trunk and extremities. Many of the cases had been clinically mistaken for Hansen′s disease prior to correct diagnosis. Marked epidermotropism and tagging of epidermis by large lymphocytes characterizes the condition histopathologically. Of the 15 cases, immunohistochemistry was possible in 10 cases, of which 8 showed predominant CD8 positive epidermotropic infiltrates and two cases showed absence of CD8 positive and CD4 positive lymphocytic infiltrate in the epidermis. Conclusion: Hypopigmented MF presents as hypopigmented asymptomatic patches without any erythema or infiltration in its early stage and mimics Hansen′s disease. Skin biopsy clinches the diagnosis

    Fibroepithelioma of Pinkus in continuity with nodular basal cell carcinoma: A rare presentation

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    Fibroepithelioma of Pinkus and nodular basal cell carcinoma (BCC) are different morphological variants of BCC. It is very rare to see both the variants together in a single lesion. Here we report a case of a 56-year-old female who presented with a nodule on the trunk, which on biopsy showed features of both nodular BCC and fibroepithelioma of Pinkus

    Zosteriform spiradenoma with spiradenocarcinoma: A rare entity

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    Eccrine spiradenoma (ES) is an uncommon well-differentiated benign tumor originating from the sweat glands. It usually occurs as a single lesion in adults. Multiple ES in a linear or zosteriform distribution are rare. Spiradenomacarcinoma is an extremely rare tumor, which develops in an existing benign spiradenoma of several years of duration. We report a case of a 23-year-old- female patient with multiple spiradenomas arranged in zosteriform pattern and malignant transformation occurred in one of the lesions over a period of 10 years
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