Identification of senescent cell surface targetable protein DPP4.

Senescent cell accumulation in aging tissues is linked to age-associated diseases and declining function, prompting efforts to eliminate them. Mass spectrometry analysis revealed that DPP4 (dipeptidyl peptidase 4) was selectively expressed on the surface of senescent, but not proliferating, human diploid fibroblasts. Importantly, the differential presence of DPP4 allowed flow cytometry-mediated isolation of senescent cells using anti-DPP4 antibodies. Moreover, antibody-dependent cell-mediated cytotoxicity (ADCC) assays revealed that the cell surface DPP4 preferentially sensitized senescent, but not dividing, fibroblasts to cytotoxicity by natural killer cells. In sum, the selective expression of DPP4 on the surface of senescent cells enables their preferential elimination.

Sphingolipid biosynthetic inhibitor L-Cycloserine prevents oxidative-stress-mediated death in an in vitro model of photoreceptor-derived 661W cells.

Oxidative stress plays a pivotal role in the pathogenesis of several neurodegenerative diseases. Retinal degeneration causes irreversible death of photoreceptor cells, ultimately leading to vision loss. Under oxidative stress, the synthesis of bioactive sphingolipid ceramide increases, triggering apoptosis in photoreceptor cells and leading to their death. This study investigates the effect of L-Cycloserine, a small molecule inhibitor of ceramide biosynthesis, on sphingolipid metabolism and the protection of photoreceptor-derived 661W cells from oxidative stress. The results demonstrate that treatment with L-Cycloserine, an inhibitor of Serine palmitoyl transferase (SPT), markedly decreases bioactive ceramide and associated sphingolipids in 661W cells. A nontoxic dose of L-Cycloserine can provide substantial protection of 661W cells against H2O2-induced oxidative stress by reversing the increase in ceramide level observed under oxidative stress conditions. Analysis of various antioxidant, apoptotic and sphingolipid pathway genes and proteins also confirms the ability of L-Cycloserine to modulate these pathways. Our findings elucidate the generation of sphingolipid mediators of cell death in retinal cells under oxidative stress and the potential of L-Cycloserine as a therapeutic candidate for targeting ceramide-induced degenerative diseases by inhibiting SPT. The promising therapeutic prospect identified in our findings lays the groundwork for further validation in in-vivo and preclinical models of retinal degeneration.

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-ß and SPL Pathways in the Human Cornea.

Human corneal fibrosis can lead to opacity and ultimately partial or complete vision loss. Currently, corneal transplantation is the only treatment for severe corneal fibrosis and comes with the risk of rejection and donor shortages. Sphingolipids (SPLs) are known to modulate fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to both, transforming growth factor beta (TGF-ß) signaling and corneal fibrogenesis. The aim of this study was to investigate the effects of sphingosine-1-phosphate (S1P) and S1P inhibition on specific TGF-ß and SPL family members in corneal fibrosis. Healthy human corneal fibroblasts (HCFs) were isolated and cultured in EMEM + FBS + VitC (construct medium) on 3D transwells for 4 weeks. The following treatments were prepared in a construct medium: 0.1 ng/mL TGF-ß1 (ß1), 1 µM sphingosine-1-phosphate (S1P), and 5 µM Sphingosine kinase inhibitor 2 (I2). Five groups were tested: (1) control (no treatment); rescue groups; (2) ß1/S1P; (3) ß1/I2; prevention groups; (4) S1P/ß1; and (5) I2/ß1. Each treatment was administered for 2 weeks with one treatment and switched to another for 2 weeks. Using Western blot analysis, the 3D constructs were examined for the expression of fibrotic markers, SPL, and TGF-ß signaling pathway members. Scratch assays from 2D cultures were also utilized to evaluate cell migration We observed reduced fibrotic expression and inactivation of latent TGF-ß binding proteins (LTBPs), TGF-ß receptors, Suppressor of Mothers Against Decapentaplegic homologs (SMADs), and SPL signaling following treatment with I2 prevention and rescue compared to S1P prevention and rescue, respectively. Furthermore, we observed increased cell migration following stimulation with I2 prevention and rescue groups, with decreased cell migration following stimulation with S1P prevention and rescue groups after 12 h and 18 h post-scratch. We have demonstrated that I2 treatment reduced fibrosis and modulated the inactivation of LTBPs, TGF-ß receptors, SPLs, and the canonical downstream SMAD pathway. Further investigations are warranted in order to fully uncover the potential of utilizing SphK I2 as a novel therapy for corneal fibrosis.

Mouse Model of Nitrogen Mustard Ocular Surface Injury Characterization and Sphingolipid Signaling.

Vesicating chemicals like sulfur mustard (SM) or nitrogen mustard (NM) can cause devastating damage to the eyes, skin, and lungs. Eyes, being the most sensitive, have complicated pathologies that can manifest immediately after exposure (acute) and last for years (chronic). No FDA-approved drug is available to be used as medical counter measures (MCMs) against such injuries. Understanding the pathological mechanisms in acute and chronic response of the eye is essential for developing effective MCMs. Here, we report the clinical and histopathological characterization of a mouse model of NM-induced ocular surface injury (entire surface) developed by treating the eye with 2% (w/v) NM solution for 5 min. Unlike the existing models of specific injury, our model showed severe ocular inflammation, including the eyelids, structural deformity of the corneal epithelium and stroma, and diminished visual and retinal functions. We also observed alterations of the inflammatory markers and their expression at different phases of the injury, along with an activation of acidic sphingomyelinase (aSMase), causing an increase in bioactive sphingolipid ceramide and a reduction in sphingomyelin levels. This novel ocular surface mouse model recapitulated the injuries reported in human, rabbit, and murine SM or NM injury models. NM exposure of the entire ocular surface in mice, which is similar to accidental or deliberate exposure in humans, showed severe ocular inflammation and caused irreversible alterations to the corneal structure and significant vision loss. It also showed an intricate interplay between inflammatory markers over the injury period and alteration in sphingolipid homeostasis in the early acute phase.

Potentiation of Sphingolipids and TGF-ß in the human corneal stroma reveals intricate signaling pathway crosstalks.

Corneal haze brought on by fibrosis due to insult can lead to partial or complete vision loss. Currently, corneal transplantation is the gold standard for treating severe corneal fibrosis, which comes with the risk of rejection and the issue of donor tissue shortages. Sphingolipids (SPLs) are known to be associated with fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to Transforming Growth Factor ß (TGF-ß) signaling and corneal fibrogenesis. This study aimed to elucidate the interplay of SPLs, specifically sphingosine-1-phosphate (S1P) signaling, and its' interactions with TGF-ß signaling through detailed analyses of the corresponding downstream signaling targets in the context of corneal fibrosis, in vitro. Healthy human corneal fibroblasts (HCFs) were isolated, plated on polycarbonate membranes, and stimulated with a stable Vitamin C derivative. The 3D constructs were treated with either 5 µM sphingosine-1-phosphate (S1P), 5 µM SPHK I2 (I2; inhibitor of sphingosine kinase 1, one of the two enzymes responsible for generating S1P in mammalian cells), 0.1 ng/mL TGF-ß1, or 0.1 ng/mL TGF-ß3. Cultures with control medium-only served as controls. All 3D constructs were examined for protein expression of fibrotic markers, SPLs, TGF-ßs, and relevant downstream signaling pathways. This data revealed no significant changes in any LTBP (latent TGF-ß binding proteins) expression when stimulated with S1P or I2. However, LTBP1 was significantly upregulated via stimulation of TGF-ß1 and TGF-ß3, whereas LTBP2 was significantly upregulated only with TGF-ß3 stimulation. Significant downregulation of TGF-ß receptor II (TGF-ßRII) following S1P stimulation but significant upregulation following I2 stimulation was observed. Following TGF-ß1, S1P, and I2 stimulation, phospho-SMAD2 (pSMAD2) was significantly downregulated. Furthermore, I2 stimulation led to significant downregulation of SMAD4. Adhesion/proliferation/transcription regulation targets, SRC, FAK, and pERK 1/2 were all significantly downregulated by exogenous S1P, whereas I2 only significantly downregulated FAK. Exogenous TGF-ß3 caused significant upregulation of AKT. Interestingly, both I2 and TGF-ß3 caused significant downregulation of JNK expression. Lastly, TGF-ß1 led to significant upregulation of sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 3 (S1PR3), whereas TGF-ß3 caused significant upregulation of only SphK1. Together with previously published work from our group and others, S1P inhibition exhibits great potential as an efficacious anti-fibrotic modality in human corneal stromal ECM. The current findings shed further light on a very complex and rather incompletely investigated mechanism, and cement the intricate crosstalk between SPLs and TGF-ß in corneal fibrogenesis. Future studies will dictate the potential of utilizing SPLs/TGF-ß signaling modulators as novel therapeutics in corneal fibrosis.

Prognostic predictors for recurrence following curative resection in grade I/II pancreatic neuroendocrine tumours.

INTRODUCTION: Pancreatic neuroendocrine tumours (pNETs) have an excellent long-term survival after resection, but are associated with a high recurrence rate. Identification of prognostic factors affecting recurrences would enable identifying subgroup of patients at higher risk of recurrences, who may benefit from more aggressive treatment. METHODS: A retrospective analysis of prospectively maintained database of patients undergoing pancreatectomy with curative intent for grade I and II pNETs between July 2007 and June 2021 was performed. Perioperative and long-term outcomes were analysed. RESULTS: A total of 68 resected patients of pNETs were included in this analysis. Fifty-two patients (76.47%) underwent pancreaticoduodenectomy, 10 (14.7%) patients had distal pancreatectomy, and 2 (2.9%) patients underwent median pancreatectomy, while enucleation was performed in 4 patients (5.8%). The overall major morbidity (Clavien-Dindo III/IV) and mortality rates were 33.82% and 2.94%, respectively. At a median follow-up period of 48 months, 22 (32.35%) patients had disease recurrence. The 5-year overall survival and 5-year recurrence-free survival (RFS) rates were 90.2% and 60.8%, respectively. While OS was unaffected by different prognostic factors, multivariate analysis showed that lymph node involvement, Ki-67 index ≥5%, and presence of perineural invasion (PNI) were independently associated with recurrence. CONCLUSIONS: While surgical resection gives excellent overall survival in grade I/II pNETs, lymph node positivity, higher Ki-67 index, and PNI are associated with a high risk for recurrence. Patients with these characteristics should be stratified as high risk and evaluated for more intensive follow-up and aggressive treatment strategies in future prospective studies.

Current radioisotopes and radiopharmaceuticals for radiosynoviorthesis: basic and applied characteristics, production and availability.

This overview describes the basic characteristics and chemistry, production and the clinical applications and use of radiopharmaceuticals pertaining to radiosynoviorthesis (RSO). In each of the case scenarios, the physical and clinical parameters that serve as determinants and govern the choice of a particular radionuclide employed for RSO are discussed. References have been drawn on the fundamentals of RSO where applicable, including a brief review of the principles and mechanism of action, the indication and efficacy of RSO in different disease conditions and suggestions set out by the current guideline recommendations.

Quality of life comparison in thyroxine hormone withdrawal versus triiodothyronine supplementation prior to radioiodine ablation in differentiated thyroid carcinoma: a prospective cohort study in the Indian population.

BACKGROUND: Thyroid withdrawal in preparation for radioiodine ablation (RIA) may have a profound impact on health-related quality of life (HRQL). Cost implications and scheduling limit the use of recombinant TSH and triiodothyronine (T3) with its shorter half-life is a conceptually attractive alternative. METHODS: Prospective cohort study design with patients having withdrawal of thyroxine (n = 37) or T3 supplementation (n = 33). HRQL was assessed using EORTC QLQ-C30, QLQ-H&N35 and modified Billewicz questionnaires. Time interval to achieve optimal TSH levels (at least 30 mIU/ml) prior to RIA was determined. RESULTS: With the exception of emotional domain (QLQ-C30 p = 0.045), LT3 supplementation did not confer significant benefit when compared to LT4 withdrawal. Target serum TSH levels was achieved in 95% of patients by week 4 post thyroidectomy. CONCLUSIONS: LT3 supplementation delivered equivocal benefit and therefore the alternate strategies to minimize the impact on HRQL of reduction in the duration of hypothyroidism in T4 withdrawal are suggested.

Sphingolipids as critical players in retinal physiology and pathology.

Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is therefore crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) has emerged as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide 1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

Combined 177 Lu-PSMA-617 PRLT and abiraterone acetate versus 177 Lu-PSMA-617 PRLT monotherapy in metastatic castration-resistant prostate cancer: An observational study comparing the response and durability.

OBJECTIVE: The aim of present study was to determine and compare the overall response rates, progression-free survival (PFS), overall survival (OS), and clinical toxicity of the combination of 177Lu-PSMA-617 radioligand therapy (PRLT) and abiraterone acetate (AA) versus 177Lu-PSMA-617 PRLT as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) patients. MATERIALS AND METHODS: The mCRPC patients who received at least one cycle of 177 Lu-PSMA-617 PRLT with or without AA therapy, were included and analyzed in the present study. The patients were divided into two major groups. Group 1 received only 177 Lu-PSMA PRLT and Group 2 received combined 177 Lu-PSMA PRLT + AA therapy. Therapeutic dose of 177 Lu-PSMA-617 PRLT was 4.4-5.55 GBq per patient per cycle administered at intervals of 10-12 weeks in both groups. The Group 2 patients additionally received a dose of 1000 mg of AA once daily and 5 mg of prednisone twice daily. Treatment response in two groups was evaluated under four broad categories (a) symptomatic, (b) biochemical (serum prostate-specific antigen level), (c) objective molecular imaging (68 Ga-PSMA-11 and 18 F-FDG PET/CT), and (d) objective anatomical imaging (computed tomography). For assessing treatment response, patients in two groups were categorized into responders (complete response [CR], partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]). The Kaplan-Meier product-limit method was used to calculate PFS and OS following first 177 Lu-PSMA PRLT in the two groups. Univariate analysis was used to compare the patients' characteristics in two groups using a χ2 or Fisher exact test. The Kaplan-Meier curves of PFS and OS between two groups were compared by using the log-rank test (p < 0.05 significant). RESULTS: A total of 58 mCRPC patients (Group 1, 38 patients and Group 2, 20 patients) were included in this study analysis. The clinical and demographic characteristics of these patients (age, Gleason score, FDG avid disease, metastatic disease burden, and average number of 177 Lu-PSMA PRLT cycles) in two groups were compared and found to be similar (p > 0.05). Post-treatment, symptomatic, biochemical, molecular, and anatomic imaging responders were found in 22 patients (58%) and 17 patients (85%), 22 patients (58%) and 16 patients (80%), 19 patients (54%) and 14 patients (78%), and 19 patients (54%) and 14 patients (78%) in Group 1 and Group 2, respectively. The median PFS of 7 months and median OS of 8 months were documented in Group 1, whereas median PFS was not reached and median OS of 16 months registered in Group 2. Transient hematological toxicity of Grades 1 and 2 was found in total seven patients (five patients in Group 1 and two patients in Group 2). On comparison of the treatment outcome between two groups, significant p value was found for symptomatic responders (58% in Group 1 vs. 85% in Group 2), median PFS (7 months in Group 1 vs. not reached in Group 2), and median OS (8 months in Group 1 vs. 16 months in Group 2), with better outcome in Group 2 patients for these variables. CONCLUSION: In the present study, the combination of 177 Lu-PSMA-617 PRLT and AA therapy showed significant improvement in mCRPC patients' symptomatic response, PFS, and OS as compared to 177 Lu-PSMA-617 PRLT monotherapy.

Long-term outcome of "Sandwich" chemo-PRRT: a novel treatment strategy for metastatic neuroendocrine tumors with both FDG- and SSTR-avid aggressive disease.

OBJECTIVE: The primary aims of this study were to evaluate the long-term outcome of a "sandwich chemo-PRRT (SCPRRT)" regimen with regard to therapeutic response rate, progression-free survival (PFS), and overall survival (OS) rates in metastatic neuroendocrine tumors (NETs) with both somatostatin receptor (SSTR)- and fluorodeoxyglucose (FDG)-avid aggressive disease. Additionally, health-related quality of life (HRQoL) scales, clinical toxicity, and association of PFS and disease control rate (DCR) with various variables were also evaluated. MATERIALS AND METHODS: A total of 38 patients of the aforementioned cohort, who received SCPRRT (at least 2 cycles of each PRRT and chemotherapy) at our institute between January 2012 and December 2018, were included and analyzed in this retrospective study. Between two cycles of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT), two cycles of oral capecitabine and temozolomide (CAPTEM) were sandwiched. Therapeutic responses following SCPRRT were assessed by using pre-defined criteria. PFS and OS after first SCPRRT were determined. Eastern Cooperative Oncology Group (ECOG) and Karnofsky score were used for evaluation of HRQoL before and after SCPPRT in all 38 patients. Any adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) of the National Cancer Institute. Associations of PFS and DCR with various variables were evaluated. RESULTS: Response (complete response and partial response) to SCPRRT was seen in 28 patients (73%), 15 patients (39%), and 16 patients (42%) on symptomatic, biochemical, and molecular imaging response evaluation criteria respectively. A total of 17 patients (45%) had anatomical imaging response with DCR of 84% based upon the RECIST 1.1 criteria. Pre-therapy mean ECOG and KPS was 2.0 and 68, which changed to 1.0 and 75 respectively following SCPRRT. Long-term follow-up data was available and ranged from 12 to 65 months after the first SCPRRT. Median PFS and OS were not reached at a median follow-up of 36 months. An estimated PFS rate of 72.5% and OS rate of 80.4% was found at 36 months. Longer PFS was dependent upon high SSTR uptake and number of CAPTEM cycle (≥ 7 cycles), absence of skeletal metastasis, and no previous external beam radiotherapy (EBRT) exposure with significant P value. Higher DCR was dependent upon absence of skeletal metastasis with significant P value. SCPRRT was tolerated well with none developing grade 4 hematotoxicity and nephrotoxicity of any grade. Anemia (grade 3), thrombocytopenia (grade 3), and leukopenia (grade 3) were noticed in 1 patient (2.5%), 2 patients (5%), and 1 patient (2.5%) respectively in this study. CONCLUSION: Thus, favorable response rates with effective control of symptoms and longer PFS and OS without high-grade or life-threatening toxicities were important observations in the present study following SCPRRT in NET patients with aggressive, both FDG- and SSTR-avid, metastatic progressive disease. The study results indicate the potential role of "sandwich chemo-PRRT" in future therapeutic algorithms of aggressive, both SSTR- and FDG-positive subset of neuroendocrine tumors.

Capecitabine-Temozolomide in Advanced Grade 2 and Grade 3 Neuroendocrine Neoplasms: Benefits of Chemotherapy in Neuroendocrine Neoplasms with Significant 18FDG Uptake.

INTRODUCTION: Capecitabine-temozolomide (CAPTEM) chemotherapy, alone or with concurrent peptide receptor radionuclide therapy (PRRT), has activity in advanced WHO grade 2 and grade 3 neuroendocrine neoplasms (NENs). The objective of this study was to evaluate the activity of the CAPTEM in patients with grade 2 and grade 3 NENs and identify prognostic factors. MATERIALS AND METHODS: A retrospective analysis of patients with metastatic grade 2 and grade 3 NENs, who were having baseline significant dual uptake on 68Ga-DOTATATE/18F-fluorodeoxyglucose (FDG)-PET-CT scan and treated with CAPTEM chemotherapy between January 2014 and December 2019 at Tata Memorial Hospital, was conducted. The clinical variables and survival data were collected. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS: A total of 68 patients received the CAPTEM regimen, of whom 29 patients (43%) received CAPTEM alone and 39 patients (57%) received concurrent PRRT. The primary sites were pancreas in 32 (47%) and small intestine in 12 (18%) patients. Mean Ki-67 index was 12.6% (range: 3-50). Forty-five patients (65%) were treatment naïve. There were no significant differences in baseline clinical variables between patients treated with CAPTEM alone or with CAPTEM-PRRT. Both regimens were well tolerated. With a median follow-up of 22.1 months, the median PFS for the entire cohort was 27.5 months. There was no statistical difference in the median PFS between patients receiving CAPTEM alone or CAPTEM-PRRT (33.7 vs. 22 months; p = 0.199). A Ki-67 index of >5% predicted for inferior PFS on multivariate analysis (24 versus 73.8 months; p = 0.04; hazard ratio -3.77; 95% confidence interval: 1.07-13.26). CONCLUSION: CAPTEM, alone or concurrent with PRRT, has a significant activity in grade 2 and grade 3 NENs with dual SSTR and 18FDG expression. A Ki-67 index >5% predicts strongly for inferior outcomes and should be further explored as a prognostic cutoff in grade 2 NENs. Early initiation of CAPTEM should be considered in this group of tumors with significant baseline 18FDG expression.

Leveraging the power of non-radium radionuclide treatments in bone metastases.

This review overviews the current status and clinical results of unsealed radionuclide therapies in skeletal metastasis. The other modes of treatment such as external bean radiotherapy and the newer receptor targeted radiopharmaceuticals tagged to alpha and beta particle emitting radionuclides have also been touched upon. With the advent of the latter in recent years, the intravenously administered radiopharmaceuticals that can be employed in the setting of skeletal metastases can be broadly categorized into (i) bone-seeking and (ii) receptor targeted specific tumor-seeking radiopharmaceuticals. The second category conceptualizes the "radionuclide based theranostics" and "precision oncology" and has the additional advantage of targeting both skeletal and non-skeletal disease and being the preferred therapy befitting the contemporary paradigm of clinical oncology.

The feasibility and safety of graded adenosine stress test for myocardial perfusion in asthmatic and/or COPD patients.

SUBJECT AND METHODS: A total of 40 patients (M:F::26:14; age range: 37-84yrs; mean: 64.1yrs) with known chronic obstructive pulmonary disease (COPD) (ranging from mild to severe), referred for a stress myocardial perfusion study, were included in this study over a period of one year. All patients underwent adenosine stress in a titrated protocol and pre-infusion of short acting bronchodilator salbutamol 2 puffs few minutes prior to start adenosine infusion. In a fraction of 26 patients, pulmonary function tests (PFT) were performed and used in addition to clinical examination to classify the severity of pulmonary obstruction. On the basis of forced expiratory volume in one second (FEV1) on PFT, 4 patients had a mild disease (FEV1 60%-80%), 17 had a moderate obstructive disease (FEV1 41%-59%) and 4 had severe COPD/asthma (FEV1 <40%) while 2 patients had normal >95% FEV1. Post-stress questionnaire to assess subjective tolerance and symptoms were undertaken for all patients. RESULTS: The results demonstrated an excellent tolerance to adenosine infusion in this group of patients, with adequate stress achieved in all. None had complaints of severe dyspnoea or respiratory distress requiring medical intervention. Thirteen patients had mild to moderate degree dyspnoea during infusion. The study included a significant number of 23 elderly patients (>65 years), who showed better tolerance than the younger patients. CONCLUSION: In this pilot study in patients with COPD who referred for myocardial perfusion scintigraphy, the feasibility and safety of adenosine in a graded protocol along with a good pre-stress assessment and a short acting bronchodilator treatment was documented.

Synchronous malignancies of thyroglossal duct cyst and thyroid gland.

Malignant involvement of thyroglossal duct cyst is rare, still rarer is the synchronous malignant involvement of the thyroid gland. Although the Sistrunk procedure is often regarded as adequate, controversy exists of the need for an additional total thyroidectomy and radioiodine ablative therapy, the decision of which depends upon the presence of (i) suspicious thyroid gland nodule; (ii) presence of lymphadenopathy; or (iii) a previous history of neck irradiation. We report a 47-year-old woman diagnosed with papillary carcinoma within a recurrent thyroglossal duct cyst with infiltration into surrounding soft tissues and a suspicious thyroid nodule of the left thyroid lobe with no regional lymph node involvement. On final histopathology, the left thyroid nodule had a follicular variant of papillary carcinoma thyroid without regional nodal involvement. The patient underwent total thyroidectomy with radioactive iodine postoperatively.

Extensive Chest Wall Tissue Loss and its Management by Vertical Rectus Abdominis Myocutaneous Flap.

Extensive electric burn around the chest in children is rare and this type of injury always poses a great challenge for its management. A 12-year-old male child with extensive electric burn of the chest wall was admitted to hospital. It was a neglected case of 9 days old burn; the young boy was in critical condition having systemic features of toxemia with widespread necrosis of the skin, subcutaneous tissues, and muscles along with exposed bones (ribs and sternum) with the risk of impending rupture of pleura through the exposed intercostal spaces. After initial resuscitation, a thorough debridement of all necrotic tissues was done. Thereafter, a superiorly based vertical rectus abdominis myocutaneous flap was harvested to cover the exposed bones and intercostal spaces. The remaining raw areas were skin grafted. The child made an excellent recovery with good outcome.

From wheelchair to walking: First case report of post-electrical burn destruction of patellar ligament with its one-stage reconstruction and restoration of function.

Electrical burn injury causing bilateral patellar ligament destruction leading to complete loss of knee extension is a very rare injury. In such situation, surgical repair or reconstruction of the patellar ligament becomes necessary to restore knee functions. Here, we present such a case of an 8-year-old boy, whose both patellar ligaments were destroyed throughout its length due to high-voltage electrical injury. His left knee joint cavity was exposed and grossly infected, but the right knee joint cavity was apparently intact. The right-sided patellar ligament was reconstructed with an ipsilateral and looped semitendinosus tendon graft and covered with a medial gastrocnemius musculocutaneous flap. The patient had an uneventful recovery, and full range of motion in the right knee joint along with good bipedal locomotion was achieved successfully.

Potential Clinical Utility of FDG-PET in Non-malignant Pulmonary Disorders: A Pilot Study.

BACKGROUND: Fluorodeoxyglucose (FDG) positron emission tomography (PET) is emerging as an important non- invasive investigation in benign pulmonary conditions too. The aim of this study was to investigate its utility in the diagnosis and monitoring of various benign pulmonary diseases. METHODS: In this prospective observational hospital-based study 50 consecutive patients (26 males) with benign lung diseases underwent computed tomography of chest followed by FDG-PET at baseline and after treatment where appropriate. The findings of FDG scan are reported in the context of clinical, histopathological, physiological and radiological findings. RESULTS: All patients showed increased FDG uptake in the lung corresponding to CT findings. Of the 9 patients with sarcoidosis stage 1 (n=1), stage 2 (n=3) and stage 3 (n=5), additional uptake in the myocardium and thyroid was noted in two patients which resulted in a change in the modality of treatment. Repeat FDG scan post-treatment showed decreased uptake in all patients which was consistent with clinico-radiologic, microbiological or spirometry findings. Increased uptake was seen in one patient with pulmonary tuberculosis (TB) and in one patient with TB mediastinal lymphadenopathy at the end of intensive phase discordant with clinical and microbiological response. Of nine cases of idiopathic interstitial pneumonias (IIPs), additional intense FDG uptake was found in two cases which corresponded to the areas of honeycombing. CONCLUSIONS: FDG-PET scan can be used as an important adjunct non-invasive investigation in diagnosing and monitoring of various benign lung conditions. It also helps in assessing whole body disease burden which may change therapeutic decisions.