Risk adjustment is crucial in comparing outcomes of various surgical modalities in patients with ileal perforation

<p>Abstract</p> <p>Background</p> <p>Using crude mortality and morbidity rates for comparing outcomes can be misleading. The aim of the present study was to compare the outcome of various surgical modalities without and with risk adjustment using Physiologic and Operative Severity Scoring for the enUmeration of Mortality and morbidity (POSSUM) score in cases of ileal perforations.</p> <p>Methods</p> <p>Prospective study on 125 patients of ileal perforations. Resection anastamosis (Group I) was done in 38 patients, primary repair (Group II) in 42 patients and 45 patients had an ileostomy (Group III). The disease severity was assessed in all patients using POSSUM score. The odds of death without and with risk adjustment using POSSUM mortality score were calculated for all groups</p> <p>Results</p> <p>Seventeen patients (14%) patients died and 99 (79%) developed postoperative complications. Using crude mortality rates Group I appeared to be the best treatment option with only 2 (5%) deaths followed by Group II with 5 (12%) deaths where as Group III had the worst outcome with 10 deaths (22%). However, Group III (ileostomy) patients had higher mean POSSUM mortality and morbidity score (55.55%, 91.33%) than Group I (28%, 75.26%) and Group II (27%, 73.59%). Taking Group I as the reference (odds ratio, OR1) odds of death were greatest in Group III (OR 5.14, p = 0.043) followed by Group II (OR 2.43, p = 0.306). With risk adjustment using POSSUM mortality score the odds of death decreased in Group III (OR 1.16 p = 0.875). For the whole group, there was a significant association between the POSSUM score and postoperative complications and deaths. Mean POSSUM mortality and morbidity score of those who died (63.40 vs.33.68, p = 0.001) and developed complications (66.32 vs.84.20, p = 0.001) was significantly higher. For every percent increase in severity score the risk of postoperative complications and death increased by 1.10 (p = 0.001) and1.06 (p = 0.001) respectively.</p> <p>Conclusion</p> <p>Despite ileostomy patients having highest crude mortality and complication rates, after risk adjustment it was equally safe. Severity of the disease rather than the surgical option had a significant impact on the outcome in patients with ileal perforations.</p

Derivation of process control strategy for biosimilar: Is it different from the way a control strategy is derived for a novel biologic?

Quality based development (QbD) has become the preferred choice for developing manufacturing process for any biologic drug. A proponent for this approach has been the US Food and Drug Association (FDA). Recently, the first QbD applications have been successfully filed with FDA. Biosimilars have also gained popularity in the recent past. Development of these drugs are very different from the way a novel biologic is developed. In the last five years, many companies around the world have started working on Biosimilars of which some companies have been able to successfully develop and get approvals for Biosimilars in both FDA and European Medicenes agency (EMA). Application of QbD for a Novel and a Biosimilar drug is quite different. By nature of the requirement for developing a Biosimilar, quality of the ‘reference product’ against which the biosimilar is being developed is considered while making decisions during process development. Though the same concepts applies for a novel drug, the target quality profile is not as defined as one can write for a Biosimilar. This is because product quality information regarding the reference product is well-known and can be thoroughly analyzed and characterized. While the targets can be easily derived for a Biosimilar, deriving a process control strategy is tough. Critical Process Parameter (CPP) is defined as a process parameter that has significant impact on the safety and efficacy of the drug. While this definition for CPP is applicable for a Bisomilar also, another aspect which requires consideration for a Biosimilar drug is the impact of process parameters on ‘fingerprint biosimilarity’. Hence the classification of process parameters as those that are critical and those that are not is not as straight forward like for a Novel drug. Derivation of acceptance range for these parameters also is different – The acceptance range for CPPs when compared to that for a novel biologic is generally found to be narrow. This is because the desired range for the outputs (such as aggregates, glycan, charge, size variants etc.) is narrow owing to the product quality ranges observed for the reference product and not just the levels of the outputs which has an effect on safety and efficacy. These subtle differences make deriving the process control strategy for a Bisomilar different from a novel biologic. In this presentation, a detailed overview of scale down model qualification, process characterization experiments, and the control strategy for Biosimilar manufacturing processes is provided. A case study will be presented which showcases some of these concepts of deriving control strategy as how it is applied for a Biosimilar process

Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application

Androgen receptor status predicts response to chemotherapy, not risk of breast cancer in Indian women

<p>Abstract</p> <p>Background</p> <p>Considerably little is known about the biological role and clinical significance of androgen receptor expression in breast cancer. The objectives of this study were to characterize <it>AR</it>-CAG repeat genotypes in a cohort of women with breast cancer and to determine the influence of AR on response to neoadjuvant chemotherapy and clinical outcome.</p> <p>Materials and methods</p> <p>Genotyping of the <it>AR </it>CAG repeat region was done on 70 patients and 80 healthy aged- matched female controls. To assess response to NACT, tissue samples from 30 LABC cases were evaluated quantitatively by real time for AR mRNA expression. The clinical response was correlated with both the pre and post chemotherapy AR expression. The CAG alleles did not show differences between cases and controls when the mean of short, long and average length of both CAG alleles was considered. However, analysis when done defining short allele as CAGn < 20 (AR1) and the long as CAGn ≥ 20 (AR2), risk was found associated with AR2 allele with marginal significance (P = 0.09). Stratification by age of onset, FH, stage, grade ER and AR status failed to reveal any association with breast cancer risk. Genotype carriers with ≥20 CAGn showed decrease of AR mRNA expression although significance could not be established (P = 0.47). Tumours in responders had the higher AR mRNA expression levels in pre neo-adjuvant chemotherapy condition (p < 0.02) which got reduced after neoadjuvant chemotherapy and the difference was found to be significant (P = 0.014).</p> <p>Conclusions</p> <p>Although, expansion of the CAGn in the <it>AR </it>gene doesn't show any major effect on breast cancer risk, patients with positive AR expression, pre neoadjuvant chemotherapy, were found to be good responders and a decrease in mRNA level of <it>AR </it>gene related to the chemotherapy-induced apoptosis could serve as an important independent predictor of response to NACT.</p

Diversity and status of migratory and resident wetland birds in Haridwar, Uttarakhand, India

Migration is the seasonal habitual movement, exhibited by many avian species along a flyway from breeding to wintering grounds and vice versa all over the world. Migratory birds are very sensitive to even small changes in water level which may be affected by flood or drought on their breeding and wintering grounds. High rains during monsoon season can cause flood conditions in the lower hills and Gangetic plains including Haridwar district. In our study, conducted during last ten years (2009-2018), we covered Bheemgoda Barrage and Missarpur Ganga Ghat of Haridwar, Uttarakhand, where 46 species of Migratory (M) and Resident Migratory (RM) wetland birds were observed. Bird survey indicated that there was a significant increase (p = 0.064, t-test) in the population of certain species such as Bhraminy Shelduck (67%), Black Headed Gull (31%), Gadwall (7%), Northern Pintail (59%), Red Crested Pochard (10%) and Tufted Pochard (47%) in Missarpur Ganga Ghat as compared to Bheemgoda Barrage (based on the average abundance of the species observed during study period). It may be pointed out that after flood and loss of vegetated island, there was significant decrease (p= 0.023, t-test) in the population of species such as Black necked stork (76%), Great crested grebe (56), Pallas gull (47%) at Bheemgoda barrage, while some species such as Bar headed goose, Common pochard did not arrive in Bheemgoda barrage after the flood. The study would help to understand the effect of climatic change on water birds species distribution in natural and man-made wetlands

Clasp knife in the gut: a case report

BACKGROUND: A wide range of foreign bodies has been retrieved from the gut and reported. The presentation may be in the form of complications like intestinal obstruction, perforation and formation of abscesses etc but there is no case report of a half open clasp knife being retrieved from the ileum, the patient having thrived, in spite of its presence for a period of eight months. CASE PRESENTATION: A 30-year-old administrative clerk had undergone emergency abdominal surgery eight months previously under mysterious circumstances at a remote district hospital and had recovered completely. Later the blade of a knife was accidentally detected when an X ray of the abdomen was done during a routine follow-up visit to his family physician. Surgery revealed a clasp knife in the ileum, which was retrieved. The presence of an entero-enteric fistula short circuiting the loop was the secret of his earlier survival. CONCLUSIONS: To the best of our information this is the first case-report of a clasp knife in the gut and of the patient thriving in spite of its presence. We report here the dramatic sequence of events

Clear cell odontogenic carcinoma: a diagnostic and therapeutic dilemma

BACKGROUND: Clear cell odontogenic carcinoma is a rare odontogenic tumor occurring in the anterior region of the mandible in 5(th)–7(th )decades and shows a female preponderance. It is potentially aggressive, capable of frequent recurrences and loco-regional and distant metastases. CASE PRESENTATION: A 45- year- old woman presented with a radiolucent left mandibular swelling associated with loss of teeth. Left cervical lymph nodes were enlarged on palpation. The patient underwent resection of the tumor but consequent to resected margins being positive for tumor cells underwent left hemimandibulectomy with ipsilateral functional neck dissection and was free of recurrence at 8 months follow-up. CONCLUSION: Clear cell odontogenic carcinoma should be considered in the differential diagnosis of jaw tumors with conspicuous clear cell component. Curettage or conservative resection inevitably results in recurrences and/or metastasis and more radical resection is warranted in these tumors, especially when they are large and show soft tissue invasion

Isolated colostomy site recurrence in rectal cancer-two cases with review of literature

<p>Abstract</p> <p>Background</p> <p>Colostomy site carcinomas are rare with only eight cases reported in the world literature. Various etiological factors like adenoma-cancer sequence, bile acids, recurrent and persistent physical damage at the colostomy site by faecal matter due to associated stomal stenosis have been considered responsible. Two such cases are being reported and in both cases there was no evidence of any local recurrence in the pelvis or liver and distant metastasis. Both patients had received adjuvant chemotherapy following surgery.</p> <p>Case presentation</p> <p>First case was a 30-year-old male that had reported with large bowel obstruction due to an obstructing ulcero-proliferative growth (poorly differentiated adenocarcinoma) at the colostomy site after abdomino-perineal resection, performed for low rectal cancer six years previously. Wide local excision with microscopically free margins was performed with a satisfactory outcome. Four years later he presented with massive malignant ascites, cachexia and multiple liver metastasis and succumbed to his disease.</p> <p>Second case was a 47-year-old male that presented with acute large bowel obstruction due to an annular growth (well differentiated adenocarcinoma) in the upper rectum. He was managed by Hartmann's operation and the sigmoid colostomy was closed six months later. Five years following closure of colostomy, he presented with two parietal masses at the previous colostomy site scar, which, on fine needle aspiration cytology were found to be well-differentiated adenocarcinomas of colorectal type. Surgery in the form of wide local resection with free margins was performed. He presented again after five years with recurrence along the previous surgery scar and an incisional hernia and was managed by wide local excision along with hernioplasty. Follow-up of nine years following first surgery is satisfactory.</p> <p>Conclusion</p> <p>Colostomy site/scar recurrence of rectal carcinoma is rare and could be due to various etiological factors, although the exact causative mechanism is not known. Surgery with microscopically free margins is recommended in the absence of metastatic disease. Stenosis of the stoma is considered as one of the most important contributory factors and should be followed carefully.</p