A multifaceted strategy using a composite of anti-cancer nanotherapeutic and natural biomaterials silk fibroin (SF) and chitosan (CS) blend scaffolds was investigated for the treatment of a tissue defect post-tumor resection by providing local release of the therapeutic and filling of the defect site with the regenerative bioscaffolds. The scaffold-emodin nanoparticle composites were fabricated and characterized for drug entrapment and release, mechanical strength, and efficacy against GILM2 breast cancer cells in vitro and in vivo in a rat tumor model. Emodin nanoparticles were embedded in SF and SFCS scaffolds and the amount of emodin entrapment was a function of the scaffold composition and emodin loading concentration. In vitro, there was a burst release of emodin from all scaffolds during the first 2 days though it was detected even after 24 days. Increase in emodin concentration in the scaffolds decreased the overall elastic modulus and ultimate tensile strength of the scaffolds. After 6 weeks of in vivo implantation, the cell density (p < 0.05) and percent degradation (p < 0.01) within the remodeled no emodin SFCS scaffold was significantly higher than the emodin loaded SFCS scaffolds, although there was no significant difference in the amount of collagen deposition in the regenerated SFCS scaffold. The presence and release of emodin from the SFCS scaffolds inhibited the integration of SFCS into the adjacent tumor due to the formation of an interfacial barrier of connective tissue that was lacking in emodin-free SFCS scaffolds. While no significant difference in tumor size was observed between the in vivo tested groups, tumors treated with emodin loaded SFCS scaffolds had decreased presence and size and similar regeneration of new tissue as compared to no emodin SFCS scaffolds.
Sir, A 36-year-old married lady was referred to our endocrine clinic by a general practitioner, on the background of three miscarriages (all first trimester), with difficult to control thyrotoxicosis (Graves’ disease), desiring pregnancy. She had one male child aged 6 years (fit and well) and was found to have an overactive thyroid gland 9 months following the delivery of her first child. Ever since her diagnosis, she had stayed poorly controlled with an occasional under-active thyroid picture (elevated TSH), bringing out the issue of poor compliance to her antithyroid therapy. Her history included intolerance to carbimazole (skin rash) because of which oral therapy was switched to propylthiouracil (PTU). She refused other options (radio-iodine therapy and surgery) of treating the thyroid. She was a vegetarian, nonsmoker, nonethanolic without any significant family history or drug history. Examination revealed an anxious, withdrawn lady with a pulse rate of 116 beats/min regular and fine tremors in both the hands. Her weight was 53 kg, with a body mass index of 21.5 kg/m2. The supine blood pressure was 140/92 mm of Hg without any postural fall. She had a goiter that was smooth without a bruit or obvious evidence of retrosternal extension. She had grade 2 eye signs. Proximal muscle weakness was 4/5 in all four limbs. General and systemic examination was otherwise normal. Biochemistry was unremarkable, except for a mild anemia (hemoglobin 10.2 gm% normocytic normochromic) and hypocalcemia (secondary to vitamin D deficiency). She had biochemical evidence of thyrotoxicosis with free T4 2.8 ng/dl (0.9–1.7); free T3 6.5 ng/dl (1.9–3.2); TSH <0.001 mIU/ml (0.4–5); anti-thyroperoxidase antibody >1000 mIU/l (<35); anti-thyroglobulin antibody 342 mIU/l (<30); and anti-TSH receptor antibody 36.3 mIU/l (0–5.6). The technetium thyroid uptake scan revealed a diffuse thyroid uptake of 16.3% (<4%) consistent with Graves’ disease. The sonography of the neck revealed an enlarged thyroid gland, but was otherwise unremarkable. She presented to us with a dose of 150 mg/day of PTU that the general practitioner had recently increased from 100 mg/day. On reviewing previous thyroid function tests, we noticed that most of the TSH levels were suppressed with the odd value suggesting over-treatment (elevated TSH). Noncompliance versus a brittle thyroid picture was the only probability and therefore in order to achieve and maintain stability of the thyroid gland, we offered her “block and replace” oral anti-thyroid therapy, using PTU and levothyroxine. By just blocking her using PTU, we could have run the potential risk of inducing an under-active thyroid and therefore opted out, assuming the sensitive obstetric history. We initiated PTU in a blocking dose of 400 mg/day (divided doses) and after 4 weeks were able to add a replacement dose of 50 μg/day of levothyroxine based on the FT3 and FT4 values keeping them in the upper range of normal. Within 8 weeks, her TSH was 0.6 mIU/l with high-normal FT3 and FT4 values. On her follow-up, she mentioned that she had missed her periods and might have been pregnant which we confirmed by a serum beta-HCG test. We monitored her thyroid function fortnightly for 1 month and then monthly till term while keeping a close eye on the liver function tests. The PTU dose was kept stable while the levothyroxine dose gradually increased to a maintenance dose of 150 μg/day till term. At approximately 28 weeks of gestation, we repeated the TSH-receptor antibody, 1.8 mIU/l (reduced from 36.3). She delivered a healthy baby boy who was monitored closely for any thyroid dysfunction. Immediately following delivery, we resumed her initial dose of PTU and levothyroxine and she continues to stay euthyroid while on the block and replace therapy. We plan to stop the block and replace therapy and treat her only with PTU with the aim of weaning her off it completely guided by the TSH-receptor antibody. A thyrotoxic biochemical picture especially due to Graves’ disease can be associated with both fatal maternal and fetal outcomes. It is therefore very important to have the thyroid function under reasonable control so as to avoid any obstetric fatalities. The maternal impact of uncontrolled thyrotoxicosis includes heart failure, pre-eclampsia, and gestational diabetes mellitus. Neonatal complications include preterm delivery, low birth weight, stillbirth, and mid-pregnancy neonatal mortality. Rarely TSH-receptor antibodies can induce a neonatal thyrotoxicosis. The optimal control of the thyroid gland in the mother is a matter of much debate, as it needs to be balanced against avoiding fetal and maternal mortality versus inducing hypothyroidism in the fetus. The current goal of antithyroid therapy in pregnant women with Graves’ disease is to maintain fT4 levels at or slightly above the normal range. This leads to minimal fetal thyroid suppression compared to maintaining fT4 within the upper third of normal as was done earlier for it often lead to low fetal cord fT4 levels, endangering hypothyroidism in the child.[1–6] By just “block-therapy” using either PTU or carbimazole, it is often difficult to keep the fT4 in the upper range of normal if the focus is primarily on keeping the TSH in the lower range. “Block and replace therapy” provides the ideal platform for preventing fetal hypothyroidism as the fT4 can be manipulated very easily exogenously while maintaining the TSH in the low normal range in the shortest timeframe possible. All antithyroidals seem to be reasonably effective in controlling maternal hyperthyroidism. The only question that arises is as to how safely it can be done. With recent reports of PTU-related liver failures, much concern has been expressed with its use throughout the gestational period. Previous recommendations for the use of antithyroidals included the use of PTU as the drug of first choice in thyrotoxicosis during pregnancy because of its proposed lower teratogenecity. However, current recommendations suggest the use of PTU in the first trimester unless contraindicated (intolerance: rash, agranulocytosis) and the use of methimazole as the drug of choice in the second and third trimester as it can rarely cause aplasia cutis, and choanal atresia when given in the first trimester.[78] The case described here is unique because contrary to current recommendations for the use of methimazole, the option could not be exercised because of the patient's intolerance to it. The usual “block and replace” therapy involves the use of neomercazole with thyroxin. There are no documented experiences of the use of the block and replace therapy in the medical literature, especially with PTU and thyroxin, and this is the first case report describing the successful use of such a combination in a pregnant lady with Graves’ disease. Although this is only a single case report, outcome studies using this therapeutic option may be useful to confirm superior maternal and fetal outcomes for pregnant ladies with Graves’ disease.
ABSTRACT Background This review article discussed the use of bridging therapy with low‐molecular‐weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI). Hypotheses Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy. Results This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population. Conclusion The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision‐making and improve patient outcomes.
Background: Congestive heart failure (CHF) is a major cause of morbidity and mortality in USA with a huge economic burden on health care. This study was done to determine the trend of hospitalizations from CHF, length of stay, mean cost of hospitalization and discharge disposition over last decade (2002-2011). Methods: We used Nationwide Inpatient Sample data to extract data for patients hospitalized with primary diagnosis of CHF using clinical classification software code of 108, corresponding to ICD 9 codes of 398.91, 428.0, 428.1, 428.20, 428.21, 428.22, 428.23, 428.30, 428.31, 428.32, 428.33, 428.40, 428.41, 428.42, 428.43, 428.9. NIS is a nationally representative survey of hospitalizations conducted by the Healthcare Cost and Utilization Project developed through a Federal-State-Industry partnership and sponsored by Agency for Healthcare Research and Quality. It represents 20% of all hospital data in US. Data was extracted for the years 2001-2011. Trend of rate of hospitalizations, mean length of st...
Background Sarcoidosis is a systemic, non-caseating granulomatous disease characterised by clinical and histopathological variability. Objective To review cases of cutaneous sarcoidosis and describe their clinical and histopathological features. Methods A retrospective study was conducted to analyse the clinical and histopathological frecords of all available skin biopsy slides signed out as 'sarcoidal tissue reaction' or 'sarcoidosis' from 2014 till 2022. Results A total of 25 cases were studied. The lesions were most commonly located on the head and neck (18 cases, 72%). Morphologically plaques (20%) were the most common, and the majority of cases had lesions of ≥2 distinct morphologies (44%). Histologically, classical naked granulomas were observed in 72% of cases. The granulomatous infiltrate was pandermal in 56% of cases, perivascular and interstitial in 16%, and perivascular, perieccrine, and interstitial in 12%. Granulomas with a 'leprosy' pattern were observed in 20% of cases. High-density granulomas (occupying >30% of the dermis) were present in 64% of cases. Fibrinoid necrosis and fibrosis between granulomas were observed in 16% and 8% cases, respectively. Inclusion bodies, such as asteroid and Schaumann bodies, were seen in 24% and 4% cases, respectively. Reticulin-rich granulomas were observed in 54% cases, while reticulin-poor granulomas were seen in 8.3%. Elevated serum ACE levels were found in 14 cases, and tuberculin skin test, conducted in 22 cases, was negative. Extracutaneous involvement was found in 11 cases, with 10 having pulmonary and 1 with pulmonary and splenic involvement. Limitation Retrospective nature of the study and small sample size. Conclusion Cutaneous sarcoidosis presents with a wide range of clinical and histomorphological features, necessitating clinico-histopathological correlation and ancillary investigations to establish the diagnosis and rule out mimickers.
An increasing number of patients require mechanical ventilation and there has been a proportional increase in patients needing prolonged mechanical ventilation (ventilated for ≥ 21 days, for atleast 6 hours per day). It accounts for about 10% of all mechanically ventilated patients. Although these patients represent a smaller proportion of intensive care unit (ICU) patients, they consume substantial ICU resources. We studied etiology, metabolic and clinical profile, complications and outcome of these patients.This was a prospective observational study in the medical ICUs of a tertiary hospital over 18 months. All patients above 12 years of age requiring prolonged invasive mechanical ventilation were recruited. Detailed clinical and laboratory records were noted. Sequential Organ Failure Assessment (SOFA) score was calculated on admission.Of a total 1150 patients who were admitted in ICU during study duration, 34.5% (n= 397) needed mechanical ventilation and 3.91% (n=45) required prolonged mechanical ventilation. Most common patient subsets were: acute inflammatory demyelinating polyneuropathy (AIDP) 28.50% (n=13), cerebro-vascular accident (CVA): 17.30% (n=8), tetanus 8.60% (n=4) and acute respiratory distress syndrome (ARDS) 6.50% (n=3). The mean age of patients was 32 years. Electrolyte imbalances observed were hypocalcaemia (84.44%), hypomagnesaemia (40.9%), hypokalemia (31.11%) and hypophosphatemia (23.8%). Ventilator-associated pneumonia (VAP) (53.33%) was the most frequent complication, followed by decubitus ulcers (40%) and deep vein thrombosis (8.89%). Mean duration of ICU stay was 57.02 days ± 44.73 days. Twenty six out of 45 patients (57.75%) were successfully weaned off ventilator support and discharged from the hospital. The SOFA score of patients who survived (mean 2.15) was lesser than that of patients who expired (mean 2.89) (p= 0.36, ns).The incidence of prolonged mechanical ventilation in our study was 3.91% of total 1150 ICU admissions and 11.3% of the 397 patients requiring invasive mechanical ventilation. AIDP, CVA, tetanus and ARDS were the most common diagnoses. Survival in the study population was 57.75%. VAP was the most common complication. High incidence of hypocalcaemia, hypomagnesaemia, hypokalemia and hypophosphatemia was noted in patients requiring prolonged mechanical ventilation.
Drug therapy is a process for cure the patient dise ases. And in this study several studies can involve such as Photodynamic therapy (PDT), Music therapy, and Chewing gum as drug delivery system. Photodynamic therapy is a relatively new procedure used for the treatment of acne. Music has frequently been used as a therapeut ic agent from the ancient times. The concept of Music Therapy is dependent on correct intonation and right use of th e basic elements of music. Chewing gum is an obvious drug delivery system for local treatment of diseases in t he oral cavity and in the throat, as sustaining the release of active substances may deliberately prolong expo sure.
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