Prescription Practices Regarding the use of Systemic Drugs in the Management of Patients with Chronic Pruritus amongst Indian Dermatologists - A Questionnaire Based Survey.

Background: Chronic pruritus poses a significant challenge to treating physicians due to multitude of underlying causes and varying treatment strategies. Several topical, systemic, and physical modalities have been tried with variable success. Prescription practices in chronic pruritus are influenced by differential knowledge and experience of physicians, patient-related factors, and resource availability. Aim: The purpose of this survey was to observe the current pattern of practice in Indian dermatologists in the management of chronic pruritus and to identify practice gaps particularly regarding the use of various systemic agents as antipruritics. Materials and Methods: A previously validated questionnaire was sent to consultant dermatologists across India between January 2020 and July 2020. The questionnaire was comprised of six questions (multiple-choice questions as well as open-ended questions) regarding the use of antidepressants, cyclic gamma-aminobutyric acid (GABA) analogues, opioid antagonists, antihistamines, and alternate therapies in the management of chronic pruritus. Results: A total of 700 dermatologists completed the questionnaire (response rate 70%). Overall, antihistamines were the most common drug prescribed in chronic pruritus (more than 95% respondents). Other systemic agents such as opioid antagonists, gabapentinoids, and antidepressants were prescribed by 22.42%, 71.85%, and 75.29% respondents, respectively, in chronic pruritus as either monotherapy or in combination with antihistamines in specific types of itches. Among antidepressants, tricyclic antidepressants (TCAs) (69.29%) were prescribed most often, followed by selective serotonin reuptake inhibitors (SSRIs) (32.29%) and serotonin and norepinephrine reuptake inhibitors (SNRIs) (9.14%). Other treatment options such as omalizumab, thalidomide, ondansetron, ursodeoxycholic acid (UDCA), and rifampicin were used by 10% respondents to alleviate pruritus in special situations. Conclusion: This survey revealed the redundant practice of prescribing antihistamines in chronic pruritus irrespective of etiology among Indian dermatologists. It also revealed a differential approach regarding use of systemic agents such as gabapentinoids, opioid antagonists, and antidepressants, in academic and non-academic institutions. The survey emphasized a barrier in writing prescription of systemic agents such as opioid antagonist and SNRIs due to lack of knowledge and experience, fear of side effects, and inadequate available evidence.

Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole.

PURPOSE: This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor-positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment. PATIENTS AND METHODS: Women age 40 to 49 with estrogen receptor-positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2), and had received tamoxifen for ≥ 1 year were treated with letrozole (2.5 mg) daily for ≥ 2 years. Serum follicle-stimulating hormone (FSH) and E2 were measured at baseline and over 2 years. A general linear model was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. RESULTS: The study enrolled 177 women (145 women age 45 to 49 years and 32 women age 40 to 44 years). Of 173 evaluable patients, 67 (39%; 95% CI, 31% to 46%) regained ovarian function; 11 of these patients (6%; 95% CI, 3% to 10%) resumed menses, and 56 of these patients (32%; 95% CI, 25% to 39%) developed premenopausal E2 without menses. Among AI-naïve patients, serial FSH significantly increased over time (P < .001), did not vary significantly by OFR status (P = .55), but showed mild evidence of a decrease after month 12 for those who resumed menses (P = .0989). Age less than 45 years and inhibin B were significant multivariable baseline predictors of OFR. CONCLUSION: These results emphasize the challenge in determining definitive menopause in women with chemotherapy-induced amenorrhea. The risk of OFR during treatment with AIs in amenorrheic women in their 40s is high, and AI therapy should be avoided in these patients.

What is the optimal rate of failed extubation?

Failed extubation (FE), defined as reintubation 48 or 72 hours after planned extubation, occurs in a significant percentage of patients and is associated with a substantial burden of morbidity and mortality. This commentary reviews the literature describing FE rates and the clinical consequences of FE and proposes an 'optimal' rate of FE as well as avenues for future research.

Single subcutaneous administration of RGDK-lipopeptide:rhPDGF-B gene complex heals wounds in streptozotocin-induced diabetic rats.

Development of effective therapeutics for chronic wounds remains a formidable clinical challenge. Deficiency of growth factors is of paramount importance among the multitude of factors contributing to the pathogenesis of diabetic wounds. Clinical interest has been witnessed in the past for exogenous applications of platelet derived growth factor B (PDGF-B) in chronic nonhealing wounds. However, accomplishing even modest favorable clinical effects in such topical applications requires large and repeated doses of PDGF-B proteins. Chronic wounds are being increasingly circumvented by gene therapy approach and to this end, cationic liposomes are emerging as promising nonviral carriers for delivering various growth factors encoding therapeutic genes to wound beds. However, as in case of topical application of growth factors, all the prior studies on the use of cationic liposomes in nonviral gene therapy of wounds involved repeated injections of cationic liposome:cDNA complexes over several weeks for ensuring complete wound healing. Herein, we show that a single subcutaneous administration of an electrostatic complex of rhPDGF-B plasmid, integrin receptor selective RGDK-lipopeptide 1 and cholesterol (as auxiliary lipid) is capable of healing wounds in streptozotocin-induced diabetic Sprague-Dawley rats (as model of chronic wounds). Western blot analysis revealed significant expression of rhPDGF-B in mouse fibroblast cells transfected with RGDK-lipopeptide 1:rhPDGF-B lipoplex. The transfection efficiencies of the RGDK-lipopeptide 1 in mouse and human fibroblast cells preincubated with various monoclonal anti-integrin receptor antibodies support the notion that the cellular uptake of the RGDK-lipopeptide 1:DNA complexes in fibroblast cells is likely to be selectively mediated by alpha5beta1 integrin receptors. Findings in the histopathological stainings using both hematoxylin and eosin (H & E) as well as Masson's Trichrome staining revealed a significantly higher degree of epithelization, keratization, fibrocollagenation and blood vessel formation in rats treated with RGDK-lipopeptide 1:rhPDGF compared to those in rats treated with vehicle alone.

Increased yield of high purity recombinant human interferon-gamma utilizing reversed phase column chromatography.

Increasing therapeutic applications for recombinant human interferon-gamma (rhIFN-gamma), an antiviral proinflammatory cytokine, has broadened interest in optimizing methods for its production and purification. We describe a reversed phase chromatography (RPC) procedure using Source-30 matrix in the purification of rhIFN-gamma from Escherichia coli that results in a higher yield than previously reported. The purified rhIFN-gamma monomer from the RPC column is refolded in Tris buffer. Optimal refolding occurs at protein concentrations between 50 and 100 microg/ml. This method yields greater than 90% of the dimer form with a yield of 40 mg/g cell mass. Greater than 99% purity is achieved with further purification over a Superdex G-75 column to obtain specific activities of from 2 x 10(7) to 4 x 10(7)IU/mg protein as determined via cytopathic antiviral assay. The improved yield of rhIFN-gamma in a simple chromatographic purification procedure promises to enhance the development and therapeutic application of this biologically potent molecule.

CD74 is expressed by multiple myeloma and is a promising target for therapy.

PURPOSE: CD74 (HLA-DR-associated invariant chain) plays a role in antigen presentation. In addition to its expression on antigen-presenting cells, it is expressed by carcinomas of renal, lung, gastric, and thymic origin and by certain sarcomas. The restricted expression of CD74 by normal tissues and its very rapid internalization make CD74 an attractive therapeutic target for both cancer and immunologic diseases. Preclinical efficacy of anti-CD74 monoclonal antibody (mAb) therapy has been demonstrated in B-lymphoma models. Because there are few validated antigenic targets in multiple myeloma, CD74 expression was examined. EXPERIMENTAL DESIGN: CD74 expression was assessed by immunohistochemistry in bone marrow biopsies of known multiple myeloma cases. Its expression was measured by flow cytometry in multiple myeloma lines, and CD74 mRNA expression was determined by reverse transcription-PCR. In addition, the in vitro antiproliferative effect of LL1 mAb was evaluated on a CD74+ multiple myeloma cell line using a [3H]thymidine incorporation assay. RESULTS: CD74 expression was observed in 19 of 22 cases of multiple myeloma, with most expressing moderate to high levels in the majority of malignant plasma cells. CD74 was expressed by most multiple myeloma cell lines, as was CD74 mRNA, at levels mirroring CD74 protein. Also, unlabeled LL1 mAb mediated in vitro growth inhibition of a CD74+ multiple myeloma cell line. CONCLUSIONS: CD74 expression is frequent in multiple myeloma, with predominant expression by the malignant plasma cells. Because anti-CD74 mAbs internalize very rapidly and LL1 mAb has shown efficacy in B-lymphoma models, CD74 represents a novel and promising target for treatment of multiple myeloma. Therefore, LL1 mAb is well suited as a carrier of radionuclides, drugs, or toxins, and also has activity as an unlabeled mAb, thereby supporting its development for this unmet need in cancer therapy.

MRI-documented spontaneous regression of cervical disc herniation: a case report and review of the literature.

Spontaneous regression of the herniated lumbar discs is a well-established phenomenon. This phenomenon of disappearance of the disc has been reported occasionally in the cervical spine and very rarely in the thoracic regions. In this article, we report the rare occurrence of spontaneous resolution of one large herniated cervical disc (C6-7) with simultaneous progression of another disc prolapse (C4-5) in a 46-year-old man.

Primary cerebral sarcoid granuloma: the importance of definitive diagnosis in the high-risk patient population.

Sarcoidosis of the central nervous system has been variously reported in 5-15% of all sarcoid patients. However, presentation of sarcoidosis as an isolated 'intracranial tumor' is rare. A 35-year-old African-American woman presented with intractable headaches. Neuroimaging revealed a tumor that was suggestive of a glioma or meningioma or metastasis. The symptoms did not respond to steroids, and an open biopsy of the lesion revealed non-caseating granuloma. A thorough work-up for systemic sarcoidosis was negative. The patient remains symptom-free at a 2-year follow-up. Primary sarcoid granuloma of the brain is rare. Once systemic disease has been excluded, early tissue diagnosis is crucial. This is particularly relevant for patients in the high-risk population before considering empirical radiosurgery.