Mucocutaneous adverse events to immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Since the approval of ipilimumab in 2011, a total of nine ICIs have gained indications for various solid and hematologic malignancies. The expanding use of ICIs in oncology underscores the need for diagnosis and treatment expertise in immune related adverse events (irAE). Cutaneous toxicities are the earliest and most common irAE in this class of therapy. In addition to the more frequent reactions including vitiligo, lichenoid dermatitis, psoriasiform dermatitis, other less common skin toxicities including bullous dermatoses, neutrophilic dermatoses, and autoimmune dermato-rheumatologic diseases have been reported. Even though less than 3% of cutaneous irAEs (irCAEs) are classified as grade 3 or higher events, irCAEs can greatly impact quality of life. Appropriate management of irCAEs is critical to avoid unwarranted interruptions or discontinuation of lifesaving immunotherapy.

Can quality keep up with quantity-Longitudinal trends in research output for the dermatology residency match.

Dermatology is one of the most competitive specialties to match into and continually draws high-achieving medical students. According to National Residency Match Program data, applicants reported an increasing number of total research products throughout the past decade. To better contextualize this trajectory, our study investigates the specific types of research items underlying this trend and the impact of applicant-specific and program-specific factors on research output. Names of matched dermatology applicants from 2009, 2011, 2014, 2016, and 2018 were collected and searched on PubMed and Google Scholar to analyze research output. Applicants were further stratified by sex, PhD status, medical school attended, geography of matched program, domestic/international status, and whether they had a home dermatology program. Matched applicants reported a mean of 7.6 research products per applicant in 2018 and, of those products, had a mean of 2.55 peer-reviewed publications per applicant. This discrepancy was observed in other years. Matched applicants from the top 20 schools and applicants from men had a significantly higher mean of peer-reviewed publications. We observed that research volume did not impact an applicant's likelihood of matching to his/her home institution. The upward trend in total research products may be misleading, because applicants increasingly resort to nonindexed research (eg, abstracts, presentations, chapters) to be competitive for dermatology residency. We also observed preliminary evidence of certain applicant-specific factors (eg, attending a top 20 medical school, sex) correlating to increased applicant publications. There is a need for a more stringent and holistic method of evaluating applicant research.

Disseminated atypical mycobacterial infection in an allogeneic stem cell transplant recipient.

Nontuberculous mycobacteria are pathogens with diverse manifestations in immunocompromised hosts. The lesser-known Mycobacterium haemophilum usually causes cutaneous infection. Diagnosis is challenging but is aided by molecular testing and multidisciplinary communication. We present an immunocompromised patient with disseminated cutaneous mycobacterial infection with digital tenosynovitis.

Characterization of Cutaneous Adverse Events Associated With PI3K Inhibitors in 11 Patients.

Introduction: Phosphoinositide 3-kinase (PI3K) inhibitors are a new class of cancer therapeutics that inhibits one or more enzymes in the PI3K/AKT/mTOR tumor growth pathway. As compared to other tyrosine kinase inhibitors, there is evidence that PI3K inhibitors have a higher incidence of severe cutaneous adverse events (CAEs) ranging from 2-21%. There is a lack of further characterization of clinical trials and management options for these CAEs. Methods: A retrospective chart review of our institution's records between January 2015 and May 2019 was conducted; electronic medical records were queried by using a pharmacy database and ICD-10 codes for patients receiving PI3K inhibitor who experienced CAEs during therapy. These CAEs were characterized by two board-certified dermatologists at a major cancer center. Results: Eleven patients were identified as having 12 cumulative CAEs. Average time to rash onset was 4 weeks, and the most common identified rashes were eczematous (25%) and morbilliform (17%). Four patients experienced a dose delay, and one patient immediately discontinued their PI3K inhibitor. Conclusion: Although most CAEs caused by PI3K inhibitors in this study were limited to grade 1-2 and were controlled with topical corticosteroids and oral antihistamines, a number of patients experienced dose impact. This highlights the dermatologist's role in managing and minimizing interruption of therapy while maintaining quality of life.

Synthesis and antimicrobial activity of pyrimidinyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles.

A new class of methylthio linked pyrimidinyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles were prepared under conventional and ultrasound irradiation methods. All the compounds were obtained in higher yields and in shorter reaction times in ultrasound irradiation method when compared with the conventional method. The title compounds were tested for antimicrobial activity. The compounds 12c and 12f exhibited promising antibacterial activity against P. aeruginosa whereas the compounds 13c and 13f showed pronounced antifungal activity against A. niger.

Green approach for the synthesis of thiophenyl pyrazoles and isoxazoles by adopting 1,3-dipolar cycloaddition methodology and their antimicrobial activity.

A variety of N-((1,3-diphenyl-5-aryl-1H-pyrazol-4-yl)sulfonyl)thiophene-2-carboxamides (7) and N-((5-aryl-3-phenylisoxazol-4-yl)sulfonyl)thiophene-2-carboxamides (8) were prepared from (E)-N-(arylethenesulfonyl)thiophene-2-carboxamides (4) adopting 1,3-dipolar cycloaddition of nitrile imines and nitrile oxides generated from araldehyde phenylhydrazones and araldoximes in the presence of iodosobenzene and CTAB followed by oxidation with I2 in DMSO. The compounds 4f, 7e, 7f, 8e and 8f showed potential antibacterial activity against B. subtilis whereas 8e and 8f exhibited potential antifungal activity against A. niger.

Synthesis and antimicrobial activity of styryl/pyrrolyl/pyrazolyl sulfonylmethyl-1,3,4-oxadiazolyl amines and styryl/pyrrolyl/pyrazolyl sulfonylmethyl-1,3,4-thiadiazolyl amines.

A new class of mono and bis heterocycles - styryl sulfonylmethyl-1,3,4-oxadiazolyl/1,3,4-thiadiazolyl amines, pyrrolyl sulfonylmethyl-1,3,4-oxadiazolyl/1,3,4-thiadiazolyl amines and pyrazolyl sulfonylmethyl-1,3,4-oxadiazolyl/1,3,4-thiadiazolyl amines were prepared from the synthetic intermediate Z-styrylsulfonylacetic acid adopting simple and well versed synthetic methodologies and studied their antimicrobial activity. Amongst all the tested compounds styryl thiadiazole 5c exhibited promising antimicrobial activity against Pseudomonas aeruginosa and Penicillium chrysogenum.

Does non-medical grade power cord compromise the safety of medical equipment?

A tertiary care 1000 bedded hospital contains more than 10,000 pieces of equipment worth approximately 41 million USD, while the power cords supplied along with the imported equipment do not comply with country-specific norms. Moreover, the local vendors procure power cords with type D/M plug to complete installation and also on-site electrical safety test is not performed. Hence, this project was undertaken to evaluate the electrical safety of all life-saving equipment purchased in the year 2013, referring to the guidelines of International Electrotechnical Commission 62353, the Association for the Advancement of Medical Instrumentation (AAMI) and National Fire Protection Association (NFPA)-99 hospital standard for the analysis of protective earth resistance and chassis leakage current. This study was done with a measuring device namely electrical safety analyser 612 model from Fluke Biomedical.

Synthesis and antimicrobial activity of amine linked bis- and tris-heterocycles.

A series of amine linked bis- and tris-heterocycles were prepared from heteroaryl cinnamamides and tested for antimicrobial activity. The compounds 11c and 12c exhibited excellent antibacterial activity while 12a and 12c displayed excellent antifungal activity.

Synthesis, antimicrobial and cytotoxic activities of pyrimidinyl benzoxazole, benzothiazole and benzimidazole.

A variety of pyrimidinyl benzoxazoles, benzothiazoles and benzimidazoles linked by thio, methylthio and amino moieties were prepared and studied their antimicrobial and cytotoxic activities. The compound pyrimidinyl bis methylthio benzimidazole 22 was a potent antimicrobial agent particularly against Staphylococcus aureus (29 mm, MIC 12.5 µg/mL) and Penicillium chrysogenum (38 mm, MIC 12.5 µg/mL). The amino linked pyrimidinyl bis benzothiazole 24 exhibited cytotoxic activity on A549 cells with IC50 value of 10.5 µM.

Synthesis and antimicrobial activity of (1,4-phenylene)bis(arylsulfonylpyrazoles and isoxazoles).

A new class of (1,4-phenylene)bis(arylsufonylpyrazoles and isoxazoles) were synthesized by 1,3-dipolar cycloaddition of nitrile imines and nitrile oxides to the 1,4-bis((E)-2-(arylsulfonyl)vinyl)benzenes in the presence of chloramine-T. Compound 7f exhibited pronounced antimicrobial activity.

N-(4-Chloro-phen-yl)-1-(5-{[(2-phenyl-ethen-yl)sulfon-yl]meth-yl}-1,3,4-oxadiazol-2-yl)methane-sulfonamide.

In the title compound, C(18)H(16)ClN(3)O(5)S(2), the dihedral angles between the oxadiazole ring and the phenyl and chloro-benzene rings are 23.4 (2) and 45.4 (2)°, respectively. The C-S-N-C and C(ox)-C-S-C (ox = oxadiazole) torsion angles are 89.3 (5) and -69.1 (3)°, respectively. A short intra-molecular C-H⋯O contact closes an S(6) ring. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, generating C(10) chains propagating in [001]. The packing is consolidated by C-H⋯O, C-H⋯π and very weak aromatic π-π stacking inter-actions [centroid-centroid separation = 4.085 (2) Å].

Synthesis, antimicrobial and cytotoxic activities of sulfone linked bis heterocycles.

A new class of sulfone linked bis heterocycles viz., pyrrolyl/pyrazolyl arylaminosulfonylmethyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, and 1,2,4-triazoles were prepared and tested for antimicrobial activity and cytotoxicity. The chloro-substituted compounds 5c, 8c and 14c showed comparable antibacterial activity to chloramphenicol against Pseudomonasaeruginosa and compound 5c exhibited comparable antifungal activity to ketoconazole against Penicilliumchrysogenum. One of the compounds, vinylsulfonyl oxadiazole showed appreciably cytotoxic activity on A549 lung carcinoma cells with an IC(50) at a concentration of 31.7 µM.

Synthesis and antimicrobial activity of amido linked pyrrolyl and pyrazolyl-oxazoles, thiazoles and imidazoles.

A new class of amido linked bis heterocycles viz., pyrrolyl/pyrazolyl-oxazoles, thiazoles and imidazoles were prepared by 1,3-dipolar cycloaddition of TosMIC and diazomethane to the respective cinnamamide derivatives and screened for antimicrobial activity. The chlorosubstituted imidazolyl cinnamamide (6c) is the most potential antimicrobial agent as it displayed strong antibacterial activity against Bacillus subtilis and antifungal activity against Penicillium chrysogenum.

Synthesis and antioxidant activity of oxazolyl/thiazolylsulfonylmethyl pyrazoles and isoxazoles.

A new class of oxazolyl/thiazolylsulfonylmethyl pyrazoles (10-13) and isoxazoles (14, 15) were prepared from the synthetically vulnerable intermediate E-styrylsulfonylacetic acid methyl ester (1) and studied their antioxidant activity.

Synthesis and biological activity of 2-(bis((1,3,4-oxadiazolyl/1,3,4-thiadiazolyl)methylthio)methylene)malononitriles.

The reactivity of ketene dithiolates in the presence of different equivalents of sodium ethoxide was studied. 2-(Bis((5-aryl-1,3,4-oxadiazol-2-yl)methylthio)methylene)malononitriles 5 and 2-(bis((5-aryl-1,3,4-thiadiazol-2-yl)methylthio)methylene)malononitriles 6 were prepared by the reaction of malononitrile with carbon disulfide and 5-aryl-2-(chloromethyl)-1,3,4-oxadiazoles 3/5-aryl-2-(chloromethyl)-1,3,4-thiadiazoles 4. The preliminary antimicrobial and antioxidant activities of the lead compounds were assayed.

Synthesis and bioassay of aminosulfonyl-1,3,4-oxadiazoles and their interconversion to 1,3,4-thiadiazoles.

A new class of oxadiazoles is prepared by treating aminosulfonylacetic acids with different carboxylic acid hydrazides. Interconversion of oxadiazoles to thiadiazoles is carried out with thiourea. The compounds are screened for antimicrobial and antioxidant activities.

Synthesis and bioassay of pyrrolyl oxazolines and thiazolines.

A new class of sulfone linked pyrrolyl oxazolines and thiazolines were synthesized from E-arylsulfonylethenesulfonylacetic acid methyl ester and studied their antimicrobial and antioxidant activities.