To the Editor: Alpha-melanocyte stimulating hormone (α-MSH) is a naturally occurring hormone produced by the anterior pituitary. It stimulates melanocytes to produce pigment (eg, tanning) and functions in appetite regulation, the immune system, and sexual arousal. Despite a ban by the United States Food and Drug Administration,1,2 commercially produced, unregulated peptide analogs of α-MSH (eg, melanotan, melanotan II) remain available for sale online and often promise consumers a safe, natural tan with minimal to no risk of side effects.

Postherpetic neuralgia (PHN) represents a type of peripheral neuropathic pruritus that occurs after an episode of shingles and is characterized by localized pain, paresthesia, and itch, termed postherpetic itch (PHI); all may simultaneously exist within the same dermatomal distribution.1 Although PHI has been reported to affect up to 58% of patients with shingles,2 its exact pathophysiologic mechanism is poorly understood, and there are no proven specific treatments. Herein, we describe the case of a patient who presented with a painful and severely pruritic ulcer located on the left side of the neck that developed in the setting of PHN refractory to conventional treatments.

Talimogene laherparepvec (T-VEC) is an oncolytic virus based on herpes simplex virus type 1 approved for intralesional treatment of advanced melanoma. In this article, we review the clinical literature on T-VEC for advanced melanoma and provide a practical approach to using T-VEC in the dermatologic surgery and oncology clinic. PubMed was used to conduct a systematic literature review of articles describing the structure, basic science, and clinical and therapeutic properties of T-VEC. The national clinical trials database was also searched for T-VEC clinical trials. Phase I to III clinical trials and early real-world experience have shown the efficacy of T-VEC in advanced melanoma as single or combination therapy with tolerable adverse effects. We conclude that with a standardized clinical approach and training, dermatologists can pave the way in using T-VEC and future oncolytic virus therapies in appropriate clinical scenarios.

Studies have shown a decrease in the match rate in general medical and primary care-focused specialties among US medical school graduates and an increase in that of subspecialties with “controllable lifestyles.” We evaluated the percentage of Harvard Medical School graduates who matched into high-income controllable lifestyle, low-income controllable lifestyle, and noncontrollable lifestyle specialties from 1994 to 2017. Using linear regression, we found that the percentage of students matching into high-income and low-income controllable lifestyle specialties has increased over time, while those matching into noncontrollable lifestyle specialties – comprised largely of primary care fields – decreased. Such trends may impact the US physician workforce composition over time, with growth of residency positions into fields such as internal medicine exceeding the matriculation of U.S. medical graduates into these positions. We examine whether future policies should focus on incentivizing students to pursue such noncontrollable lifestyle specialties by highlighting controllable lifestyle elements within these fields and emphasizing alternative rewards which may attract candidates to these pursuits. Keywords: RESIDENCY SPECIALTY CHOICE TRENDS, CONTROLLABLE LIFESTYLE, INCOME LEVEL, CAREER CHOICE

Tissue resident memory T cells (TRM) are non-recirculating memory T cells residing at epithelial sites which confer tissue-wide pathogen alarm and inflammatory recall. Here we identify broad expression of immune checkpoint transcripts programmed cell death protein 1 (PD-1), CTLA-4, and TIGIT on TRM across multiple viral infections and peripheral tissue sites in mouse. We find PD-1 expression is rapidly upregulated within 72 hours of viral priming in all memory-forming subsets after vaccinia viral infection but is contracted in TCM/TEM populations by 4 weeks. In contrast to prior reports, we find PD-1 protein expression is retained on a large fraction of CD69+CD103+/-TRM when tested at 5 and 6 weeks. PD-1 is expressed in steady state human skin TRM and on TRM accumulating in skin isolated from DPCP (diphenylcyclopropenone)-treated patients, above placebo, at 120 days post treatment. Because the PD-1 cognate ligand PD-L1 (CD274) is highly enriched on skin-derived DCs in mouse and human we tested the impact of PD-L1 and PD-L2 (CD273) loss on TRM-based recall against melanoma. We find an acute and transient loss of PD-L1 and PD-L2 in ZBTB46-dependent classical DCs during TRM recall significantly contracts tumors growth and improves overall survival. These results support classical DCs as a critical regulator of TRM-based recall and a dynamic role for the PD-L1/PD-L2:PD-1 axis.

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal

Patients with cancers frequently experience sleep and circadian dysfunction. To date, only a few studies have used both a questionnaire and actigraphy for concomitant evaluation of sleep and circadian function in patients with cancer. We sought to evaluate objective sleep and circadian parameters in metastatic colon cancer (MCC) patients and their associations with symptoms and quality of life (QOL).

Ms. Haitz is from Harvard Medical School, Boston, Massachusetts. Dr. Mikailov is from the Department of Dermatology, Beth Israel Deaconess Medical Center, Boston. Dr. Carter is from the Department of Dermatology, Massachusetts General Hospital, Boston. The authors report no conflict of interest. Correspondence: Karyn Haitz, BA, 107 Avenue Louis Pasteur, Mailbox 320, Boston, MA 02115 (karyn_haitz@hms.harvard.edu).

Lobular capillary hemangiomas, also known as pyogenic granulomas, are common, benign, vascular proliferations of the cutaneous or mucous surfaces that grow rapidly and are prone to ulceration and bleeding.1Lin R.L. Janniger C.K. Pyogenic granuloma.Cutis. 2004; 74: 229-233PubMed Google Scholar, 2Harris M.N. Desai R. Chuang T.Y. Hood A.F. Mirowski G.W. Lobular capillary hemangiomas: an epidemiologic report, with emphasis on cutaneous lesions.J Am Acad Dermatol. 2000; 42: 1012-1016Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Recurrence of lobular capillary hemangiomas in the same location after treatment is common with rates ranging from 3.7% to 43.5%.3Lee J. Sinno H. Tahiri Y. Gilardino M.S. Treatment options for cutaneous pyogenic granulomas: a review.J Plast Reconstr Aesthet Surg. 2011; 64: 1216-1220Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar Well-known causes of lobular capillary hemangiomas are trauma, infection, medication, chronic irritation, viral oncogenes, increased levels of female sex hormones, and microscopic arteriovenous anastomoses.1Lin R.L. Janniger C.K. Pyogenic granuloma.Cutis. 2004; 74: 229-233PubMed Google Scholar Patients commonly seek treatment because of associated pain or discomfort from ulceration, bleeding, or both. Surgical excision and cryotherapy show best therapeutic outcomes for lobular capillary hemangiomas, although electrodessication, shave excision, imiquimod cream, topical timolol, and sclerotherapy are also used.3Lee J. Sinno H. Tahiri Y. Gilardino M.S. Treatment options for cutaneous pyogenic granulomas: a review.J Plast Reconstr Aesthet Surg. 2011; 64: 1216-1220Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 4Khorsand K. Maier M. Brandling-Bennett H.A. Pyogenic granuloma in a 5-month-old treated with topical timolol.Pediatr Dermatol. 2015; 32: 150-151Crossref PubMed Scopus (19) Google Scholar We report a case of frequent lobular capillary hemangioma development in the setting of von Hippel-Lindau syndrome (VHL) and neurofibromatosis type 1 (NF1), requiring multiple treatment modalities. A 34-year-old man with a history of VHL and NF1 was referred to dermatology for evaluation and management of multiple bleeding papules. The papules were tender, and the bleeding caused his pillowcases to be soaked in blood. He reported many similar papules previously in various anatomical locations. Removal of prior lesions was successful and did not cause satellitosis. New papules would appear gradually over years, and at the time of the visit, 6 papules were bothersome because of intermittent bleeding. The patient was given the diagnosis of NF1 based on clinical findings that were first noted in childhood including multiple café au lait macules, axillary freckling, and Lisch nodules. VHL was suspected after magnetic resonance imaging showed hemangioblastoma of the left cerebellum during evaluation of sensorineural hearing loss. VHL was subsequently confirmed by mutation analysis (P81S mutation). Central nervous system hemangioblastoma is the most common tumor in VHL and was present in the patient. He did not have any additional tumors or cysts in the central nervous system or visceral organs that are common in VHL, which include retinal hemangioblastomas, renal cell carcinoma and cysts, pheochromocytomas, and pancreatic tumors and cysts.5Lonser R.R. Glenn G.M. Walther M. et al.von Hippel-Lindau disease.Lancet. 2003; 361: 2059-2067Abstract Full Text Full Text PDF PubMed Scopus (1100) Google Scholar The patient did not have family history of NF1 or VHL. Medications included dextroamphetamine for attention deficit disorder. On physical examination, the lesions of concern were exophytic, red, vascular papules located on the right jawline, front of the right shoulder, left lower aspect of the back, and right lower aspect of the back, consistent with lobular capillary hemangiomas (Fig 1). These were painful with slight pressure. Several other similar, although smaller, papules were noted on the trunk. On the face, trunk, and extremities there were at least 20 scattered well-defined, ovoid, light-brown macules. Involving the chest, abdomen, and back were multiple discrete 4- to 8-mm subcutaneous rubbery-soft nodules (Fig 2). Axillary freckling was noted on both axilla and the groin. The patient returned to the dermatology clinic 4 months later with new growing and bleeding vascular papules in new locations; they were similar to those removed at the initial visit and consistent with lobular capillary hemangiomas.Fig 2Multiple café au lait macules, axillary freckling, and neurofibromas on the torso and abdomen.View Large Image Figure ViewerDownload (PPT) There are many options for treatment of lobular capillary hemangiomas. In our patient, these lesions were treated by shave excision with electrodessication and samples were sent for histologic evaluation (Fig 3). At the follow-up visit 4 months later, 5 additional lesions were destroyed with the same approach. Neither recurrence nor satellitosis was noted at sites of prior treatment. NF1 and VHL are both autosomal dominant syndromes caused by mutations of tumor suppressor genes with prevalences of 1:3,000 and 1:36,000 respectively.5Lonser R.R. Glenn G.M. Walther M. et al.von Hippel-Lindau disease.Lancet. 2003; 361: 2059-2067Abstract Full Text Full Text PDF PubMed Scopus (1100) Google Scholar, 6Lu-Emerson C. Plotkin S.R. The neurofibromatoses. Part 1: NF1.Rev Neurol Dis. 2009; 6: E47-E53PubMed Google Scholar The presence of 2 independent genetic syndromes in the same individual is extremely rare, and this case represents a chance event rate of 1 in 108,000,000 (based on the combined prevalence of VHL 1:36,000 and NF1 1:3000).5Lonser R.R. Glenn G.M. Walther M. et al.von Hippel-Lindau disease.Lancet. 2003; 361: 2059-2067Abstract Full Text Full Text PDF PubMed Scopus (1100) Google Scholar, 6Lu-Emerson C. Plotkin S.R. The neurofibromatoses. Part 1: NF1.Rev Neurol Dis. 2009; 6: E47-E53PubMed Google Scholar NF1 occurs as a result of mutation of the NF1 tumor suppressor gene (chromosome 17), leading to neurofibromas, café au lait macules, central nervous system gliomas, and bony abnormalities.6Lu-Emerson C. Plotkin S.R. The neurofibromatoses. Part 1: NF1.Rev Neurol Dis. 2009; 6: E47-E53PubMed Google Scholar VHL occurs as a result of a mutation in the VHL tumor suppressor gene (chromosome 3), which leads to unregulated growth of vascular tumors in multiple tissues. Common VHL tumors include hemangioblastomas of the retina, brain, and viscera along with renal cell carcinoma and pheochromocytoma.5Lonser R.R. Glenn G.M. Walther M. et al.von Hippel-Lindau disease.Lancet. 2003; 361: 2059-2067Abstract Full Text Full Text PDF PubMed Scopus (1100) Google Scholar, 7Maher E.R. Neumann H.P. Richard S. von Hippel-Lindau disease: a clinical and scientific review.Eur J Hum Genet. 2011; 19: 617-623Crossref PubMed Scopus (447) Google Scholar In VHL, angiogenesis is likely the result of increased levels of glucose transporter 1, vascular endothelial growth factor, and platelet-derived growth factor.5Lonser R.R. Glenn G.M. Walther M. et al.von Hippel-Lindau disease.Lancet. 2003; 361: 2059-2067Abstract Full Text Full Text PDF PubMed Scopus (1100) Google Scholar Unlike in NF1, VHL does not exhibit cutaneous findings.8Quigg M. Rust R.S. Miller J.Q. Clinical findings of the phakomatoses: von Hippel-Lindau disease.Neurology. 2006; 66: E33-34Crossref PubMed Scopus (4) Google Scholar Interestingly, lobular capillary hemangiomas have not been described in association with either NF1 or VHL. This patient shows an uncommon growth pattern of lobular capillary hemangiomas with numerous lesions in new locations that require periodic treatment for symptom relief rather than the typical recurrent lobular capillary hemangioma in the same location. Based on known predisposing factors of lobular capillary hemangiomas and based on the pathophysiology of this patient's genetic diseases, we hypothesize that increased vascular endothelial growth factor in addition to minor trauma contributed to this presentation (Fig 4). We present a case of a patient with VHL and NF1, and very frequent development of lobular capillary hemangiomas. We hypothesize that this phenomenon is related to the angiogenesis pathways induced by VHL. Further studies are needed to examine a connection between VHL and/or NF1 and lobular capillary hemangiomas.

410 Background: Sleep disruption is a prevalent problem among cancer patients and survivors, but clinical correlates of poor sleep are understudied, especially in colorectal cancer. We recently showed that metastatic breast cancer patients with poor sleep efficiency have a shorter overall survival. The primary study objective is to clarify the relationship between subjective sleep disruption and survival in patients with metastatic colorectal cancer (MCC). Methods: 240 pts (63% male, mean age=59; SD=11.0) treated for MCC in 1st to 5th line of 5-fluorouracil based chemotherapy completed the QOL Questionnaire (EORTC QLQ-C30). We considered sleep to be disrupted if patients reported little to severe trouble sleeping (scores >0 ). Multivariate Cox models included age, gender, site of primary tumor, stage at diagnosis, number of metastatic sites, performance status and prior chemotherapy. Results: 65.4% of the patients reported mild to severe sleep disruption according to EORTC QLQ-C30. Patients with trouble sleeping had poorer overall survival as compared to those without sleep disruption (HR: 1.47 [1.11 to 1.95]; p=0.008). Respective median survival times (months) were 14.2 [95% CI: 12.3 to 16.1] and 17.7 [10.0 to 25.3]. The survival benefit observed in patients without sleep disruption remained statistically significant after adjustment for other prognostic factors. The final multivariate prognostic model included subjective sleep disruption (HR: 1.49 [1.11 to 2.00]; p=0.009), number of metastatic sites (p<0.001), performance status (p=0.023), and prior chemotherapy (p<0.001). Conclusions: Our findings show that patients reported sleep disruption is an independent prognostic factor for overall survival in MCC. Future research is needed to determine the mechanisms of sleep disruption and its effect on survival, and whether treatment of sleep disruption can improve survival in MCC.

STUDY DESIGN: Repeated-measures clinical measurement reliability study.OBJECTIVES: To establish the reliability and face validity of the Functional Lower Extremity Evaluation (FLEE).BACKGROUND: The FLEE is a 45-minute battery of 8 standardized functional performance tests that measures 3 components of lower extremity function: control, power, and endurance. The reliability and normative values for the FLEE in healthy athletes are unknown.METHODS: A face validity survey for the FLEE was sent to sports medicine personnel to evaluate the level of importance and frequency of clinical usage of each test included in the FLEE. The FLEE was-then administered and rated for 40 uninjured athletes. To assess test-retest reliability, each athlete was tested twice, 1 week apart, by the same rater. To assess interrater reliability, 3 raters scored each athlete during 1 of the testing sessions. Infraclass correlation coefficients were used to assess the test-retest and interrater reliability of each of the FLEE tests.RESULTS: In the face validity survey, the FLEE tests were rated as highly important by 58% to 71% of respondents but frequently used by only 26% to 45% of respondents. lnterrater reliability intraclass correlation coefficients ranged from 0.83 to 1.00, and test-retest reliability ranged from 0.71 to 0.95.CONCLUSION: The FLEE tests are considered clinically important for assessing lower extremity function by sports medicine personnel but are underused. The FLEE also is a reliable assessment tool. Future studies are required to determine if use of the FLEE to make return-to-play decisions may reduce reinjury rates.