Polymer-Based Drug Delivery Systems for Cancer Therapeutics.

Chemotherapy together with surgery and/or radiotherapy are the most common therapeutic methods for treating cancer. However, the off-target effects of chemotherapy are known to produce side effects and dose-limiting toxicities. Novel delivery platforms based on natural and synthetic polymers with enhanced pharmacokinetic and therapeutic potential for the treatment of cancer have grown tremendously over the past 10 years. Polymers can facilitate selective targeting, enhance and prolong circulation, improve delivery, and provide the controlled release of cargos through various mechanisms, including physical adsorption, chemical conjugation, and/or internal loading. Notably, polymers that are biodegradable, biocompatible, and physicochemically stable are considered to be ideal delivery carriers. This biomimetic and bio-inspired system offers a bright future for effective drug delivery with the potential to overcome the obstacles encountered. This review focuses on the barriers that impact the success of chemotherapy drug delivery as well as the recent developments based on natural and synthetic polymers as platforms for improving drug delivery for treating cancer.

Update of penetrance estimates in Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic syndrome caused by pathogenic or likely pathogenic germline variants in the FLCN gene. Patients with BHD syndrome have an increased risk of fibrofolliculomas, pulmonary cysts, pneumothorax and renal cell carcinoma. There is debate regarding whether colonic polyps should be added to the criteria. Previous risk estimates have mostly been based on small clinical case series. METHODS: A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN. Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants. RESULTS: Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers. CONCLUSIONS: These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.

Surgical Field Quality in Trans-Nasal Endoscopic Surgeries Using Lignocaine Infusion and Dexmedetomidine Infusion. A Prospective Randomized Control Study.

Trans-nasal endoscopic surgery (TNES) is a helpful diagnostic and therapeutic modality in otorhinolaryngology surgeries and requires controlled hypotension for better visualization of the surgical field. Recent literature shows evidence of intravenous Lignocaine infusion to produce the controlled hypotension. The study aims to assess and compare the effects of Lignocaine (LIG) and Dexmedetomidine (DEX) infusion with respect to surgical field quality. 101 Consenting adult patients undergoing elective TNES were double-blinded, randomly allocated in one of the two groups and received either DEX infusion of 0.5ug/kg/hr (n = 51) or LIG infusion of 1.5 mg/kg/h (n = 50) after a loading dose. Surgical field score (SVF) as the primary outcome and secondary outcomes such as variations in hemodynamic parameters, the requirement for rescue agents and total blood loss were recorded. Both the groups were comparable with respect to patient demographics, total duration of anesthesia and surgery. SVF scores were significantly better in the LIG group during the first 105 min of the surgery (p < 0.05). In response to intubation, hemodynamic parameters were lower in LIG group. The requirement of other adjuvant drugs, total blood loss (166.40 ml vs. 251.17 ml) and extubation time were also significantly lower in the LIG group. The study concludes that intravenous Lignocaine gives a better surgical field in the first 105 min of surgery, comparable hemodynamics and decreased blood loss in patients undergoing TNES as compared to Dexmedetomidine infusion. Hence its role as an agent for controlled hypotension during TNES surgery is promising.

Batch Fabrication of a Polydimethylsiloxane Based Stretchable Capacitive Strain Gauge Sensor for Orthopedics.

Polymer-based capacitive strain gauges are a novel and promising concept for measuring large displacements and strains in various applications. These novel sensors allow for high strain, well above the maximum values achieved with state-of-the-art strain gauges (Typ. 1%). In recent years, a lot of interest in this technology has existed in orthopedics, where the sensors have been used to measure knee laxity caused by a tear of the anterior cruciate ligament (ACL), and for other ligament injuries. The validation of this technology in the field has a very low level of maturity, as no fast, reproducible, and reliable manufacturing process which allows mass production of sensors with low cost exists. For this reason, in this paper, a new approach for the fabrication of polymer-based capacitive strain gauges is proposed, using polydimethylsiloxane (PDMS) as base material. It allows (1) the fast manufacturing of sensor batches with reproducible geometry, (2) includes a fabrication step for embedding rigid electrical contacts on the sensors, and (3) is designed to produce sensor batches in which the size, the number, and the position of the sensors can be adapted to the patient's anatomy. In the paper, the process repeatability and the robustness of the design are successfully proven. After 1000 large-strain elongation cycles, in the form of accelerated testing caused much higher strains than in the above-mentioned clinical scenario, the sensor's electrical contacts remained in place and the functionalities were unaltered. Moreover, the prototype of a patient customizable patch, embedding multiple sensors, was produced.

Assessment of Impairment of Quality of Life in Foot Eczema and Correlation thereof with Epidemiological Data of its Patients: A Cross-Sectional Study.

BACKGROUND: Eczema of foot adversely impacts daily activities, work productivity, and interpersonal relationships. MATERIALS AND METHODS: This cross-sectional, questionnaire-based study collated epidemiological data of 70 outpatients of foot eczema, evaluated their quality of life by 10-item dermatology life quality index (DLQI) questionnaire, and undertook the correlation thereof. RESULTS: Cases were predominantly males (48; 68.5%); 26 (37.1%) belonged to fifth decade of life and 47 (67%) presented within 12 months of onset. Dorsa of feet was involved in most (59; 84.2%) cases. Itching was a universal complaint followed by scaling (51; 72.9%), dryness (22; 31.4%), and oozing (21; 30%). History of atopy was reported by 15 (21.4%) patients; tobacco and/or alcohol abuse 32 (45.7%) patients; past treatment was received by 37 (52.9%) patients; and winter aggravation in 9 (12.3%) patients. Mean DLQI score was 13.64; with very large effect (11-20) on QoL in 38 (54.3%) patients; moderate (6-10) in 15 (21.4%) patients; extremely large (21-30) in 9 (12.9%) patients; and small (2-5) in 8 (11.4%) patients. Mean scores of questions of DLQI tool were 2.46 in first question (symptoms), 1.99 in fifth (social activities); 1.81 in seventh (working/studying); and 0.17 in fourth (clothes) question. Significant (P < 0.05) impairment of quality of life emerged with respect of burning, scaling, oozing, history of atopy, seasonal variation, and past treatment. CONCLUSION: Our study reports significant association of atopy, winter aggravation, past treatment, burning, scaling, and oozing with adverse quality of life in our study on cases of foot eczema and appears to be first study from India.

A prospective randomized trial of xylometazoline drops and epinephrine merocele nasal pack for reducing epistaxis during nasotracheal intubation.

BACKGROUND: The most frequent complication of nasotracheal intubation (NTI) is epistaxis. Epinephrine nasal gauze packing has been used conventionally as a pre-treatment for reducing epistaxis, but it carries a disadvantage of pain and anxiety in patients. However, xylometazoline drops are easier to administer and more convenient for patients. We aimed at comparing the effectiveness of xylometazoline drops and epinephrine merocele packing in reducing bleeding and postoperative complications in our population. METHODS: Our study enrolled 120 patients in a double-blind randomized controlled trial. We randomly allocated ASA1 or 2 adult patients into 2 groups: Group X and Group E. Group X received 0.1% xylometazoline nasal drops, and epinephrine (1:10,000) merocele nasal packing was used in Group E. The primary outcome was the incidence of bleeding during NTI; the severity of bleeding, navigability, bleeding during extubation, and postoperative complications were secondary outcomes. We used IBM SPSS and Minitab software for statistical analysis, and P < 0.05 was considered statistically significant. RESULTS: We analyzed the data of 110 patients: 55 in Group X and 55 in Group E. The two groups did not have different bleeding incidence (56.4% vs 60.0%; P = 0.70); however, the incidence of severe bleeding was less with xylometazoline than with epinephrine (3.63% vs 14.54%; P < 0.05). We also observed less bleeding during extubation (38.2% vs 68.5%; P < 0.05) with xylometazoline. Other secondary outcomes were akin to both groups. CONCLUSION: The incidence of severe and post-extubation bleeding was significantly less with xylometazoline. Hence, it may be an effective alternative for reducing the incidence and severity of epistaxis during NTI.

Comparative Analysis of Epidemiological Data as Well as Quality of Life in Patients having Hand Eczema vis-à-vis Foot Eczema.

CONTEXT: Eczema of hand or foot though not life-threatening, not only impacts daily activities and work productivity adversely, but also impairs interpersonal relationships. MATERIALS AND METHODS: Cross-sectional study of 100 outpatients of hand and foot eczema at a tertiary care teaching institute. Epidemiological data was collated and quality of life (QoL) evaluated by dermatology life quality index (DLQI) score. RESULTS: Forty seven had hand eczema, 45; foot eczema and 8; both. Peak incidence of hand eczema (38.2%) was in fourth decade and foot eczema (33.3%), fifth decade. Hand eczema was more frequent in females (32; 68%) and foot eczema in males (32; 71.1%). Hand eczema was more common among housewives (14; 29.7%) and foot eczema among manual labourers (26; 57.7%). A persistent course was seen in foot (44; 83%) whereas recurrent course in hand eczema (21; 38.1%). Aggravation on contact with irritants/allergens was associated more with hand (32; 58.1%) than with foot eczema (18; 33.9%). Association with atopy was not significant. Substance abuse was associated more with foot eczema (25; 47.1%). Impairment in QoL was significantly higher in hand eczema (mean DLQI, 16.33) as compared to foot eczema (12.83). CONCLUSION: Hand eczema prevalent among females showed a high rate of recurrence whereas foot eczema in males, has a persistent course. Atopy is not significantly associated. The impairment in QoL is much greater in hand eczema as compared to foot eczema. The studies on comparative analysis of hand vis-à-vis foot eczema do not appear to exist in literature whereas studies of QoL impairment on hand eczema are abound.

Carcinoma cervix de novo with widespread cutaneous/subcutaneous metastasis: A rare case report.

Cancer of the uterine cervix is one of the leading gynecological malignancies of developing nations including India. A 45-year-old female presented with menstrual irregularities and other nonspecific symptoms. After initial workup, she was diagnosed with carcinoma cervix, Stage IV A, while she was being planned to take up radical concomitant chemoradiotherapy, she developed widespread nodules over various sites over the body, which were histopathologically proven as metastatic lesions. She was treated with a palliative intent by radiotherapy and chemotherapy. Only a few such cases have been reported in the literature with variable outcomes. These rare presentations should be thoroughly worked up and studied to know more about their biological behavior.

Evaluating awareness and practices pertaining to radioactive waste management among scrap dealers in Delhi, India.

OBJECTIVES: With nuclear technology rapidly taking the spotlight in the last 50 years, radiation accidents seem to be a harsh reality of the modern world. The Mayapuri Radiation accident of 2010 was the worst radiation accident India has yet dealt with. Two years thereafter, we designed a study to assess the awareness and practices regarding radioactive waste among scrap dealers aiming to assess deficiencies in radiation disaster preparedness. METHODOLOGY: A community based cross-sectional study. The study population consisted of 209 volunteers (from 108 scrap dealerships) including 108 shop-owners and 101 workers segregated as Group A consisting of 54 dealerships in Mayapuri and Group B of 54 dealerships from the rest of the city. Subjects were then interviewed using a semi-structured questionnaire. RESULTS: Awareness about radioactive waste varied significantly with level of education (p = 0.024), Kuppuswamy's socio-economic scale (p = 0.005), age of the scrap dealer (p = 0.049) and his work experience (p = 0.045). The larger dealerships in Mayapuri were more aware about radioactive waste (p = 0.0004), the accident in 2010 (p = 0.0002), the symbol for radiation hazard (p = 0.016), as well as the emergency guidelines and the agencies to contact in the event of a radiation accident. CONCLUSIONS: Our findings seem to signify that while governmental and non-governmental agencies were successful in implementing prompt disaster response and awareness programs, the community continues to be inadequately prepared. These go on to suggest that though concerted awareness and training programs do benefit the affected community, economic and social development is the key to disaster prevention and mitigation.

Congenital syphilis: The continuing scourge.

Congenital syphilis is a severe, disabling infection that occurs due to the transmission of Treponema pallidum across the placenta during pregnancy or from contact with an infectious genital lesion during delivery. However, its early diagnosis is often difficult because more than half of the affected infants are asymptomatic, and the signs in symptomatic infants may be subtle and nonspecific. Although its incidence is declining, this long-forgotten disease continues to affect pregnant women, resulting in considerable perinatal morbidity and mortality. We hereby report a case of a 2-month-old infant with early congenital syphilis presenting with joint swellings and Parrot's pseudoparalysis, a comparative rarity in the present scenario. The report also stresses upon the importance of implementing the Centres for Disease Control and Prevention recommendation that all the pregnant women should be screened for syphilis in the first antenatal visit in the first trimester and again in late pregnancy.

Triads in dermatology.

It is imperative for any dermatology resident to have a good knowledge of the various triads in dermatology. For an easy grasp over this topic, we have grouped the various triads on the basis of their etiologies.

Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy.

Despite significant advancements with recombinant AAV2 or AAV8 vectors for liver directed gene therapy in humans, it is well-recognized that host and vector-related immune challenges need to be overcome for long-term gene transfer. To overcome these limitations, alternate AAV serotypes (1-10) are being rigorously evaluated. AAV5 is the most divergent (55% similarity vs. other serotypes) and like AAV1 vector is known to transduce liver efficiently. AAV1 and AAV5 vectors are also immunologically distinct by virtue of their low seroprevalence and minimal cross reactivity against pre-existing AAV2 neutralizing antibodies. Here, we demonstrate that targeted bio-engineering of these vectors, augment their gene expression in murine hepatocytes in vivo (up to 16-fold). These studies demonstrate the feasibility of the use of these novel AAV1 and AAV5 vectors for potential gene therapy of diseases like hemophilia.

Epidermodysplasia verruciformis: an unusual malignant transformation.

Epidermodysplasia verruciformis (EV) is a rare, life-long heritable disease caused due to a unique susceptibility to human papilloma virus. The disseminated verrucous lesions and pityriasis versicolor-like lesions persist from early childhood and can transform into a cutaneous malignancy in a fourth of patients. Malignant transformation into syringoid eccrine carcinoma (SEC) has been reported only once so far. SEC is an extremely invasive, rare, locally destructive, slowly growing adnexal tumor. We hereby report the association of EV with SEC in a 29-year-old male.

Clinical spectrum of cleidocranial dysplasia: a case report.

BACKGROUND: Cleidocranial dysplasia is a developmental anomaly of the skeleton and the teeth. This condition may be inherited, be transmitted as dominant characteristics in either sex, or even may appear spontaneously. It presents with skeletal defects of several bones, like partial or complete absence of clavicles, late closure of the fontanels, presence of open skull sutures and multiple wormian bones. CASE PRESENTATION: In this case report, we describe an otherwise healthy 30 year-old male with a chief complaint of missing anterior maxillary and Mandibular teeth. CONCLUSION: Cleidocranial dysplasia is very rare in occurrence, incidence being 1: 1,000,000. Since early diagnosis of cleidocranial dysplasia is essential for initiating the appropriate treatment approach, clinicians should be aware of the characteristic features. We report a case of cleidocranial dysplasia because of its rarity.

The role of interstitial brachytherapy using template in locally advanced gynecological malignancies.

OBJECTIVE: Brachytherapy plays a major role in the treatment of patients with carcinoma of the cervix. However, routine intracavitary brachytherapy may not be feasible or adequate to treat locally advanced disease. The purpose of this prospective study was to assess treatment outcome for patients with locally advanced gynecological malignancies treated with interstitial brachytherapy using Martinez Universal Perineal Interstitial Template (MUPIT) and to study the acute and late sequelae after treatment by this technique. METHODS: Thirty previously untreated patients with histologically confirmed carcinoma of the cervix (20 patients), vault (7 patients), and vagina (3 patients) were treated by a combination of external beam radiotherapy using megavoltage irradiation to the pelvis to a dose of 4000 to 5000 cGy followed by interstitial brachytherapy using MUPIT between June 2000 to August 2001 at Gujarat Cancer and Research Institute, Ahmedabad. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitary radiotherapy was found to be unlikely to encompass the tumor volume were treated with interstitial template brachytherapy using MUPIT applicator and were enrolled for this study. Criteria for inclusion in this study were as follows: Hemoglobin--minimum 10 gm%; Performance Status--70% or more (Karnofsky Scale); Histopathological confirmation; FIGO Stage--IIb-IIIb (excluding frozen pelvis). RESULTS: Among the 30 patients studied, 4 lost to follow-up and they were excluded from the study. With a median follow up of 9 months, local control was achieved in (20/26) 76.92% patients. The local control was better for nonbulky tumors compared to bulky tumors irrespective of stage of disease. Local control rate was better in patients with good regression of disease after EBRT. The time gap between EBRT and implant also had an impact on the outcome. CONCLUSION: Interstitial template brachytherapy by MUPIT is a good alternative to deliver high-dose radiation in locally advanced gynecological malignancies where conventional brachytherapy application is either not feasible or unlikely to encompass tumor volume adequately. The locoregional control obtained is definitely better than external beam therapy alone and within the accepted range of complications. However, long-term follow-up is needed to comment on late morbidities.