Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy.

BACKGROUND: The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single-session stereotactic radiosurgery (SRS) and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. PATIENTS AND METHODS: Patients were included if MBMs were treated with single-session SRS within 3 months of receiving systemic therapy. The primary end point of this study was distant MBM control. Secondary end points were local MBM control defined as a >20% volume increase on follow-up MRI, systemic progression-free survival, overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. RESULTS: Ninety-six patients were treated to 314 MBMs over 119 SRS treatment sessions between January 2007 and August 2015. No significant differences were noted in age (P = 0.27), gender (P = 0.85), treated gross tumor volume (P = 0.26), or the diagnosis-specific graded prognostic assessment (P = 0.51) between the treatment cohorts. Twelve-month Kaplan-Meier (KM) distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (P = 0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the KM local MBM control rates among treatment groups (P = 0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared with conventional chemotherapy. CONCLUSION: In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.

A novel radiographic technique to asses grafts in the female -pelvis: a comparison of the Inside-Out and the Outside-In trans-obturator mid urethral sling positioning.

UNLABELLED: The three-dimensional configuration of mid-urethral sling tapes is difficult to demonstrate in traditional anatomical dissections or imaging studies. The aim of this study was to test the utility of a novel technique using mesh tapes to assess spatial differences between the in-out and out-in transobturator mid-urethral slings. Two independent surgeons performed their usual transobturator mid-urethral sling placement on 10 fresh thawed cadavers, alternating sides in the consecutive cadavers. Tantalum wires threaded through the polypropylene-tapes rendered them radio-opaque. Following placement, CT scans were obtained to generate 3-D and MIPS images for analysis. Results showed that the mean angle formed by the in-out sling measured 122º (95%CI: 107º-136º); versus 144º (95%CI: 131º-151º) for the out-in sling (p = 0.02). The paired differences between the tapes' inner angles were significantly different; with a mean difference of 20º (median 19.0º), (p = 0.008). There was no significant correlation between either approach and BMI or angle of the pubic arch. The images revealed that the tapes lie as a band posterior/dorsal to the urethra rather than inferior. IN CONCLUSION: marking mesh with -Tantalum wire, in combination with 3-D and MIPS CT-scan reconstruction images, provided a unique method to visualize the entire sling trajectory. The clinical implications of the more horizontal positioning after the out-in approach remain to be determined.

Argyreia speciosa (Linn. f.) sweet: A comprehensive review.

Argyreia speciosa (Linn. f.) Sweet is a popular Indian medicinal plant, which has long been used in traditional Ayurvedic Indian medicine for various diseases. This plant is pharmacologically studied for nootropic, aphrodisiac, immunomodulatory, hepatoprotective, antioxidant, antiinflammatory, antihyperglycemic, antidiarrheal, antimicrobial, antiviral, nematicidal, antiulcer, anticonvulsant, analgesic and central nervous depressant activities. A wide range of phytochemical constituents have been isolated from this plant. A comprehensive account of the morphology, phytochemical constituents and pharmacological activities reported are included in view of the many recent findings of importance on this plant.

Sphaeranthus indicus Linn.: A phytopharmacological review.

Sphaeranthus indicus Linn. (Asteraceae) is widely used in Ayurvedic system of medicine to treat vitiated conditions of epilepsy, mental illness, hemicrania, jaundice, hepatopathy, diabetes, leprosy, fever, pectoralgia, cough, gastropathy, hernia, hemorrhoids, helminthiasis, dyspepsia and skin diseases. There are reports providing scientific evidences for hypotensive, anxiolytic, neuroleptic, hypolipidemic, immunomodulatory, antioxidant, anti-inflammatory, bronchodialatory, antihyperglycemic and hepatoprotective activities of this plant. A wide range of phytochemical constituents have been isolated from this plant including sesquiterpene lactones, eudesmenolides, flavanoids and essential oil. A comprehensive account of the morphology, phytochemical constituents, ethnobotanical uses and pharmacological activities reported are included in this review for exploring the immense medicinal potential of this plant.

Drug use in pregnancy; a point to ponder!

Pregnancy is a special physiological condition where drug treatment presents a special concern because the physiology of pregnancy affects the pharmacokinetics of medications used and certain medications can reach the fetus and cause harm. Total avoidance of pharmacological treatment in pregnancy is not possible and may be dangerous because some women enter pregnancy with medical conditions that require ongoing and episodic treatment (e.g. asthma, epilepsy, hypertension). Also during pregnancy new medical problems can develop and old ones can be exacerbated (e.g. migraine, headache) requiring pharmacological therapy. The fact that certain drugs given during pregnancy may prove harmful to the unborn child is one of the classical problems in medical treatment. In 1960's pregnant ladies who ingested thalidomide gave birth to children with phocomalia. Various other examples of teratogenic effects of drugs are known. It has been documented that congenital abnormalities caused by human teratogenic drugs account for less than 1% of total congenital abnormalities. Hence in 1979, Food and Drug Administration developed a system that determines the teratogenic risk of drugs by considering the quality of data from animal and human studies. FDA classifies various drugs used in pregnancy into five categories, categories A, B, C, D and X. Category A is considered the safest category and category X is absolutely contraindicated in pregnancy. This provides therapeutic guidance for the clinician. This article focuses on various aspects relating to drug use during pregnancy.

Closer to an ideal solution for inguinal hernia repair: comparison between general surgeons and hernia specialists.

BACKGROUND: It is accepted a priori that specialists of hernia surgery have better results than general surgeons who use the same or different techniques as part of their complete surgical repertoire. METHODS: Results of general surgeons trained in the technique of hernia repair using a bilayer connected mesh device (BCMD) was compared to results of specialists and other general surgeons who used other techniques. RESULTS: One report from hernia specialists and three additional reports from trained general surgeons showed similar results using a BCMD. These results were better than results of all other mesh repairs. DISCUSSION: This study shows the value of surgeon-training as well as the value in the design of a particular mesh device for hernia repair. The three components of this device offer three separate, yet connected, barriers to the formation of a recurrent hernia. CONCLUSION: General surgeons trained to use a bilayer mesh device repeatedly duplicated the results of specialists who used it.

Cryoablation for carcinoma of the prostate.

Percutaneous transperineal cryoablation of the prostate is now available in the armamentarium for treatment of prostate cancer. Technical advances in real-time transrectal imaging of the prostate and improvements in cryosurgical equipment have brought this modality into the limelight of available prostate cancer management. Cryosurgery can be offered to many patients with prostate cancer. However, the main indications for its use include primary treatment for localized disease, salvage therapy after failure of traditional methods, and relief of local symptoms. A historical background, description of the technique, and clinical experience at several medical centers including the University of California San Diego, Allegheny General Hospital, University of Texas M.D. Anderson Cancer Center, and Crittenton Hospital, are presented.

The release and percutaneous permeation of anthralin products, using clinically involved and uninvolved psoriatic skin.

The release and permeation of 1% Westragel and 1% Westrastick and three commercial 1% anthralin products were investigated in vitro with the use of a Franz diffusion cell unit. An inert Teflon membrane with a mesh opening of 74 mu was used for measuring the rate of release. Involved psoriatic and uninvolved human skin collected from the same subjects were used for the permeation study. The permeation of danthron and dianthrone, the major degradation products of anthralin, was also studied with the use of microemulsion gels of 1% danthron and 1% dianthrone, which were prepared in the same way as 1% Westragel. The penetrating anthralin, danthron, and dianthrone were stabilized by a modified receptor fluid, and sample solutions were analyzed by a high-power liquid chromatography method. Involved psoriatic skin was found to be much more permeable to anthralin than was uninvolved psoriatic skin. The slow permeation rate of anthralin, danthron, and dianthrone through normal skin and uninvolved skin indicates that the stratum corneum is the rate-limiting barrier. In involved psoriatic skin, the release rate of anthralin from the topical product becomes the rate-determining step. Large individual variations were found in the permeation of anthralin through involved psoriatic skin, suggesting that the permeation rate of anthralin also may depend on the disease state of psoriatic patients. The anthralin molecule, possessing both hydrophilic and lipophilic centers, diffused significantly faster than did danthron and dianthrone. Westragel, 1%, showed the highest diffusion rate as well as the highest driving force when compared to other commercial 1% anthralin products. This suggests that 1% Westragel may be an optimal design, especially for short-contact anthralin therapy.

Hookworms and the species infecting man in Zambia.

The rate of hookworm infections, determined by stool examination over a 7-month period, was 16.56% in medical examinees and 19.91% in in-patients in an urban hospital population in Zambia. The egg-load though was low. Culture of ova to the filariform larval stage, examination of adult worms expelled after anthelminthic treatment and collected at autopsy confirmed that the dominant species was Necator americanus. However, we report, perhaps for the first time, the presence of Ancylostoma duodenale in man in Zambia. Such information is important in assessing the clinical significance of hookworm infection in the country and for formulating a rational chemotherapeutic policy. No cases of infection with the 'false' hookworm Ternidens deminutus were identified.

A double-blind controlled trial of metronidazole suppositories in children undergoing appendicectomy.

A total of 133 children, aged 16 months to 15 years (mean 6.7 years), with presumptive acute appendicitis, was included in a double-blind, placebo-controlled trial of the short-term (72 hour) use of metronidazole suppositories as prophylaxis against post-operative infection. There was no significant difference in the incidence or severity of wound infection or post-operative intra-abdominal sepsis between the metronidazole-treated and placebo groups. It is suggested that intra-rectal metronidazole, when used exclusively, is not sufficient for effective prophylaxis for appendicitis in childhood.

Strongyloides fülleborni infections in man in Zambia.

Rhabditiform larvae, and in two cases eggs, of Strongyloides spp. identified in the stools of Zambian patients were cultured to the free-living adult stage. Free-living adults of S. fülleborni, a parasite common in primates in Africa and Asia, were present in cultures from 13 (9.9%) of 131 cases of strongyloidiasis. In three of these cases, both S. fülleborni and S. stercoralis free-living adults were found.