Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study.

BACKGROUND: Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients. PATIENTS AND METHODS: Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks [q2w]), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w × 4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response. RESULTS: Patients were randomly assigned to receive durvalumab (n = 240), durvalumab plus tremelimumab (n = 247), or SoC (n = 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72-1.08; P = 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85-1.26; P = 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9-43.1), 30.4% (24.7-36.3), and 30.5% (24.7-36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade ≥3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. CONCLUSION: There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02369874.

Inflammatory myofibroblastic tumor in the retromolar region of an 8-year-old child: A rare finding.

Inflammatory myofibroblastic tumor (IMT) of the oral cavity is an extremely rare finding. The etiology and pathogenesis of IMT is controversial and unclear. The tumor requires complete surgical excision and continuous monitoring of clinical consequences. The present article describes the clinical, histological, operative and immunohistochemical features of a case of IMT in the mandibular retromolar region of an 8-year-old male. Histologically, the lesion shows myofibroblastic spindle cell proliferations with infiltrative margins in an inflammatory background. Immunohistochemically, the myofibroblastic spindle cells in the present case were positive for α-smooth muscle actin and CD68 due to which the diagnosis of IMT was confirmed.

SpermCheck Fertility, an immunodiagnostic home test that detects normozoospermia and severe oligozoospermia.

BACKGROUND: A simple and inexpensive home sperm test could be of considerable value to couples attempting to conceive and to men curious about their fertility potential. A two-strip lateral flow immunochromatographic diagnostic device that allows men to evaluate their sperm count at low cost in the privacy of their own homes is described. METHODS: The ability of SpermCheck Fertility to predict sperm counts obtained using a hemacytometer procedure based on standard World Health Organization methodology was assessed. Test results obtained by lay users were also compared with those obtained by trained laboratory professionals, and the ease of use of the device was evaluated in consumer studies. RESULTS: A total of 225 semen samples were analyzed in the method comparison, and the performance of SpermCheck Fertility was excellent with over 96% of all samples correctly classified as normozoospermic (> or =2 x 10(7) sperm/ml), oligozoospermic (5 x 10(6)-2 x 10(7) sperm/ml) or severely oligozoospermic (<5 x 10(6) sperm/ml). Consumer studies with 164 lay users demonstrated that SpermCheck Fertility was easy to use. Lay users and laboratory professionals agreed 95% of the time when reading the same test independently. Overall, the correct response rate on a 20-question survey about the test was over 97%. CONCLUSIONS: SpermCheck Fertility is a simple and reliable immunodiagnostic test that can quickly inform men as to whether their sperm count is normal, low or very low. This home test can assist couples in deciding whether to seek comprehensive clinical evaluation of the fertility status of the male partner.

Copper and ceruloplasmin levels in relation to total thiols and GST in type 2 diabetes mellitus patients.

Presence of oxidative stress in type 2 diabetes mellitus (DM) is well proved. Current study was undertaken to know the relation between fasting plasma glucose (FPG) and copper along with antioxidants like total thiols and ceruloplasmin, and antioxidant enzyme glutathione S transferase (GST). The study group consisted of a total of 201 subjects which included nondiabetic healthy control subjects (n = 78) and diabetic patients (n = 123). Plasma total thiols, GST, copper and ceruloplasmin levels were measured all the subjects using spectrophotometric methods and FPG levels were determined in clinical chemistry analyzer Hitachi 912. There was significant increase in FPG (P<0.001) and copper (P<0.001) and decrease in ceruloplasmin (P<0.001) and protein thiols (P<0.001) in type 2 DM cases compared to healthy controls. There was no significant change in GST between type 2 DM cases and controls. There was significant negative correlation of FPG with antioxidants like ceruloplasmin (r = -0.420, P<0.001) and total thiols (r = -0.565, P<0.001). Protein thiols correlated positively with ceruloplasmin (r = 0.364, P<0.001). Our study indicates possible increase in copper mediated generation of ROS leading to increased consumption of available antioxidants in the body.

Clinical deterioration despite syringomyelia resolution after successful foramen magnum decompression for Chiari malformation - Case series.

INTRODUCTION: Neurosurgical treatment is recommended for symptomatic syringomyelia and the post-operative radiological resolution of the syringomyelia is associated with an improvement or at least stability of the patient's pre-operative symptoms. METHODS: We reviewed syringomyelia treatment in our centre over the last five years for clinical outcome, surgical complications, post operative MRI and long term symptom resolution. RESULTS: 50 cases of symptomatic syringomyelia underwent foramen magnum decompression and expansile watertight duroplasty. While the outcomes for majority are similar to what published in literature, three of them developed typical syringomyelia symptoms after initial good recovery and radiological resolution of syrinx. CONCLUSION: Syringomyelia symptoms may appear or worsen following successful surgical treatment and radiological resolution of syrinx and it is important to counsel young people and their family regarding this.

Frontal convexity primary lymphoma masquerading meningioma: a case report and review of literature.

Primary non-Hodgkin's lymphoma of the skull with extra- and intracranial extension without systemic or skeletal manifestation in a nonimmunocompromised patient is extremely rare. These lesions often cause difficulty in diagnosis because they mimic other conditions. We report a case of primary lymphoma involving scalp, skull vault, meninges and invading the brain parenchyma and masquerading clinically and radiologically as a meningioma.

Management of Complex Ovarian Cysts in Newborns - Our Experience.

AIMS: To analyse the clinical presentation, clinicopathological correlation and management of complex ovarian cysts in newborn and infants. MATERIALS AND METHODS: Over a period of 6 years (2009-2015), 25 newborns who were diagnosed to have ovarian cyst on antenatal ultrasound, were followed up. We collected data in the form of clinical features, radiological findings, pathology and mode of treatment. RESULTS: Of the 25 fetuses who were diagnosed to have ovarian cysts, fourteen (56%) underwent spontaneous regression by 6-8 months. Eight were operated in newborn period while 3 were operated in early infancy. Seven had ovarian cyst on right side, 4 had on left side. Eight babies underwent laparoscopy while 3 underwent laparotomy. Histopathology showed varied features of hemorrhagic cyst with necrosis and calcification, serous cystadenoma with hemorrhage, benign serous cyst with hemorrhage and simple serous cyst. Post-operative recovery was uneventful in all. CONCLUSION: All the ovarian cysts detected antenatally in female fetuses need close follow-up after birth. Since spontaneous regression is known, only complex or larger cysts need surgical intervention, preferably by laparoscopy. Majority of the complex cysts show atrophic ovarian tissue hence end up in oophorectomy but simple cysts can be removed preserving normal ovarian tissue whenever possible.

Commodity scale production of sugars from starches.

The production of sugars from starch sources is an industry that exists in its present form due to the application of industrial enzymology to solve process related problems. As the industry matures, the demand for more efficient enzymes leading to higher quality products and lower production costs for the starch processor has increased. Researchers are now finding or tailoring enzymes for specific operational needs of the processor using a combination of tools such as protein engineering, directed evolution and improved accessing of natural diversity.

Neurological manifestations of Hansen's disease and their management.

Hansen's disease is almost eliminated from developed countries but in developing countries of Africa, Asia and Latin America leprosy is still considered to be a public health problem. Mycobacterium leprae have the affinity for peripheral nerves and neuropathy is a cardinal manifestation of the disease. The nerve damage affects sensory, motor, and autonomic fibers resulting in the physical impairments and limitation of physical activities and social participation. Leprosy is a curable disease and treatment provided in the early stages will avert the disabilities. Approach to the neuritic leprosy depends on its clinical characteristics, nerve biopsy, and histological appearance of dermatological and neurological lesions. In this article we review the literature and discuss the pathology, clinical features, diagnosis and management of neurological manifestations of leprosy.

Specific immunoneutralization of FSH leads to apoptotic cell death of the pachytene spermatocytes and spermatogonial cells in the rat.

Although requirement for follicle stimulating hormone (FSH) in the initiation of spermatogenesis is well documented, its role in adult spermatogenesis is still debated. In the present communication, we have investigated the effect of specific immunoneutralization of FSH on apoptotic cell death in the testicular germ cells both in immature and adult rats. The germ cells of control animals showed predominantly high molecular weight DNA while the antiserum (a/s) treated group showed DNA fragmentation characteristic of apoptosis. The pattern could be detected within 24 hours of a/s treatment, and became more pronounced after 48 hours. The germ cells were purified from FSH a/s treated rats by centrifugal elutriation and vulnerability of each cell type to undergo apoptosis on FSH neutralization was investigated. The pachytene spermatocytes were found to be most sensitive to absence of FSH, even in the adult animals suggesting the involvement of FSH in spermatogenesis. The in situ analysis of DNA strand breakage following FSH a/s treatment showed fragmentation of the DNA of the pachytene spermatocytes confirming this observation. The in situ analysis also showed that the spermatogonia undergo apoptosis in addition to the pachytene spermatocytes. These data clearly demonstrate the role of FSH in the adult rat spermatogenesis.

Mucinous cystic neoplasm of the pancreas with high carcinoembryonic antigen.

A large mucinous cystic neoplasm of the pancreas was found that showed a remarkably high carcinoembryonic antigen (CEA) level in cyst content. Staining for CEA was also detected in the lining epithelium. These findings indicate that columnar epithelial cells secrete CEA that accumulates in the cyst. We suggest that a CEA level determination of the cyst fluid, along with CEA immunoperoxidase staining on cell preparations, may prove useful in providing an accurate diagnosis of pancreatic cystic tumors.

Bacterial clearance with WHO--recommended multidrug regimen for multibacillary leprosy.

Sixty multibacillary leprosy patients with an average initial bacteriological index (BI) of 2.5 were followed up after they had completed the WHO--recommended multidrug therapy regularly till attaining bacteriological negativity. The minimum duration of treatment was two years as stipulated by WHO and the maximum duration for reaching negativity was seven years (mean 4.25 years). The minimum time for the attainment of bacteriological negativity was one year and the maximum was 6.75 years (mean 3.75 years). The higher the initial BI the longer was the time taken for the attainment of bacteriological negativity. The average fall of BI per year was 0.67. Dapsone monotherapy received before the commencement of MDT, prednisolone received during therapy and the type of leprosy did not have any effect on the time taken for bacteriological clearance. There was no relapse during the period of observation (mean 2.83 years). The site to attain negativity last was the ear lobe, in 95% of the cases.

Knowledge, attitude and practices of the community and patients regarding leprosy in Mangalore--a study.

To get acquainted with the knowledge, attitude and practices of the community and the patients towards leprosy so as to evolve a suitable health education programme, a study was conducted in Mangalore as per the schedule prepared for the purpose. The information so collected has been summarised below. Very few people among the community know that leprosy is caused by a germ (8%). Knowledge regarding this was slightly better (22%) among patients. Only 15% of the community members and 42% of the patients were aware of the early signs of the disease. 54% of the community members and 41% of the patients felt that leprosy is contagious. 60% of the community and 86% of the patients were of the opinion that leprosy is curable. Many believe that leprosy is associated with deformities and disabilities (community 64%, patients 76%). Most of the community members (79%) and patients (88%) said it is necessary to attend a hospital for treatment when leprosy is suspected. 60% of the community members and 56% of the patients felt that it is necessary to segregate leprosy patients. The findings are highlighted and discussed in the article.

Collusion and entanglement in the therapy of a patient with multiple personalities.

S.'s therapy demonstrates some of the ways in which countertransference interferes with therapy of a case presenting with multiple personalities. Fascination with S.'s alter personalities and the desire to prove their genuineness, made her therapist search for them and then repeatedly invoke their appearance. Part of the reason was his inexperience with such cases that induced him to "play it by the book," and use "personality-centered procedures" (looking for a different part, giving it a name, speaking to it, etc.) that have yet to be scientifically validated, instead of adhering to the basic principles of psychotherapy. At a deeper level, however, his excessive preoccupation with S.'s personalities was one kind of collusion with her resistance to deal with the focal issue of her sexual ambivalence. Proof of this resistance also surfaced later as a motivated shift of focus in therapy, and a weakening of the therapeutic alliance. By the time this was evident, sabotage of therapy had already occurred.

Acropigmentation of dohi.

A 9-year-old girl with multiple hyperpigmented and hypopigmented macules over the hands and neck since childhood is reported.

A rare case of bilateral tubal pregnancy.

Diagnosis of ectopic pregnancy continues to be an important challenge. Here a case of incidental diagnosis of bilateral tubal ectopic pregnancy is reported. There was a ruptured tubal ectopic pregnancy on the left side and chronic ruptured tubal ectopic pregnancy on the right side. Leading cause of first trimester maternal deaths is due to complications of ectopic pregnancy. Here an unusual case of ectopic pregnancy is reported in which the patient had spontaneous bilateral tubal ectopic pregnancy which presented with left tubal rupture and subsequently emergency exploratory laparotomy revealed bilateral tubal mass, which on histopathological examination confirmed tubal pregnancy.

Sublingual misoprostol: a better choice for cervical priming before manual vacuum aspiration.

BACKGROUND: Misoprostol is effective for cervical priming before manual vacuum aspiration (MVA). Aim of study was to determine whether sublingual misoprostol with a shorter interval of 2 hours before MVA would be as effective as its standard vaginal administration. STUDY DESIGN: This randomized control trial included 82 women randomly assigned to receive 400 mcg of misoprostol, either sublingually or vaginally. MVA was performed 2 hours and 3 hours after in sublingual and vaginal group, respectively. RESULTS: Cervical dilatation of 8 mm was achieved within 2 hours in sublingual group. Mean time taken for procedure (14.4 ± 5.3: sublingual group and 16.2 ± 5.7: vaginal group), and blood loss was comparable (12.2 ± 9.7 ml in sublingual group and 13.7 ± 8.5 ml in vaginal group). CONCLUSION: 2 hour of cervical priming with 400 mcg of sublingual misoprostol before MVA was as good as 3 hours with vaginal administration of the same dose.

Production of ethanol from winter barley by the EDGE (enhanced dry grind enzymatic) process.

BACKGROUND: US legislation requires the use of advanced biofuels to be made from non-food feedstocks. However, commercialization of lignocellulosic ethanol technology is more complex than expected and is therefore running behind schedule. This is creating a demand for non-food, but more easily converted, starch-based feedstocks other than corn that can fill the gap until the second generation technologies are commercially viable. Winter barley is such a feedstock but its mash has very high viscosity due to its high content of beta-glucans. This fact, along with a lower starch content than corn, makes ethanol production at the commercial scale a real challenge. RESULTS: A new fermentation process for ethanol production from Thoroughbred, a winter barley variety with a high starch content, was developed. The new process was designated the EDGE (enhanced dry grind enzymatic) process. In this process, in addition to the normal starch-converting enzymes, two accessory enzymes were used to solve the beta-glucan problem. First, beta-glucanases were used to hydrolyze the beta-glucans to oligomeric fractions, thus significantly reducing the viscosity to allow good mixing for the distribution of the yeast and nutrients. Next, beta-glucosidase was used to complete the beta-glucan hydrolysis and to generate glucose, which was subsequently fermented in order to produce additional ethanol. While beta-glucanases have been previously used to improve barley ethanol production by lowering viscosity, this is the first full report on the benefits of adding beta-glucosidases to increase the ethanol yield. CONCLUSIONS: In the EDGE process, 30% of total dry solids could be used to produce 15% v/v ethanol. Under optimum conditions an ethanol yield of 402 L/MT (dry basis) or 2.17 gallons/53 lb bushel of barley with 15% moisture was achieved. The distillers dried grains with solubles (DDGS) co-product had extremely low beta-glucan (below 0.2%) making it suitable for use in both ruminant and mono-gastric animal feeds.

Disseminated cutaneous rhinosporidiosis.

Rhinosporidiosis is a granulomatous disorder caused by Rhinosporidium seeberi. It frequently involves the nasopharynx and occasionally affects the skin. We hereby report a case of 46-year-old male who presented with multiple cutaneous plaque-like lesions with nasal obstruction. On examination, multiple cutaneous lesions were found to be present on malar aspect, infraorbital and supraorbital region, right shoulder and over the back near the tip of scapula. Oral cavity revealed a polypoidal lesion, in the base of the tongue. Excision biopsy confirmed the lesions as disseminated cutaneous rhinosporidiosis. The patient was treated with excision and dapsone therapy. After 1 year of therapy, the patient has disease-free survival. We report this rare case of rhinosporidiosis with disseminated cutaneous involvement.