Association Between Immunosuppression and Outcomes in Oral Cavity Squamous Cell Carcinoma.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
OBJECTIVE: To assess the effect of immunosuppression on recurrence and mortality outcomes in oral cavity squamous cell carcinoma (SCC) after initial surgical treatment.STUDY DESIGN: Retrospective cohort study.SETTING: A single academic tertiary referral center.METHODS: Patients with oral cavity SCC treated with initial surgery were included. Immunosuppressed versus nonimmunosuppressed groups were compared. Primary end points were 5-year overall recurrence and all-cause mortality. Secondary end points were recurrence subtypes (local, regional, and distant) and disease-specific mortality.RESULTS: Of 803 patients with oral cavity SCC, 71 (9%) were immunosuppressed from therapeutic drug use (n = 48) or systemic disease (n = 23). The immunosuppressed group consisted of patients with a history of transplant (21%), autoimmune or pulmonary disorder (45%), hematologic malignancy or myeloproliferative disorder (30%), and HIV infection (3%). After adjusting for baseline variables of age, sex, comorbidities, pathologic tumor characteristics, and adjuvant treatment, all recurrence and mortality outcomes were worse in the immunosuppressed group. The multivariate-adjusted hazard ratio for overall recurrence was 2.16 (95% CI, 1.50-3.12; P < .01), and all-cause mortality was 1.79 (95% CI, 1.15-2.78; P < .01) in Cox regression analysis. The 2 groups were then matched in a 1:5 ratio according to the same baseline variables. All end points apart from disease-specific mortality were significantly worse in the immunosuppressed group after matching.CONCLUSION: This study demonstrates that immunosuppression is associated with poor outcomes in oral cavity SCC, with an approximate 2-fold increase in rates of recurrence and mortality. Future studies are needed to assess the risks and benefits of adjusting therapeutic immunosuppression in this population.
View details for DOI 10.1177/0194599820960146
View details for PubMedID 32957854
Tracheostomy in Infants in the Neonatal Intensive Care Unit.
2020; 21 (5): e323–e334
Approximately half of all pediatric tracheostomies are performed in infants younger than 1 year. Most tracheostomies in patients in the NICU are performed in cases of chronic respiratory failure requiring prolonged mechanical ventilation or upper airway obstruction. With improvements in ventilation and management of long-term intubation, indications for tracheostomy and perioperative management in this population continue to evolve. Evidence-based protocols to guide routine postoperative care, prevent and manage tracheostomy emergencies including accidental decannulation and tube obstruction, and attempt elective decannulation are sparse. Clinician awareness of safe tracheostomy practices and larger, prospective studies in infants are needed to improve clinical care of this vulnerable population.
View details for DOI 10.1542/neo.21-5-e323
View details for PubMedID 32358145
Primary Care-Based Skin Cancer Screening in a Veterans Affairs Health Care System.
Skin cancer screening may improve melanoma outcomes and keratinocyte carcinoma morbidity, but little is known about the feasibility of skin cancer training and clinical skin examination (CSE) by primary care practitioners (PCPs) in large health care systems.To assess the association of skin cancer training and screening by PCPs with dermatology referral patterns and rates of skin biopsies.In this pilot interventional study performed at the Veterans Affairs Palo Alto Health Care System, patients 35 years or older scheduled for an annual health habits screen in the PCP general medicine clinics were studied.Six PCPs underwent Internet Curriculum for Melanoma Early Detection (INFORMED) training in May 2015, and 5 screened patients during the following 14 months.Proportion of dermatology referrals, subsequent skin biopsies, and PCP diagnostic accuracy for skin cancer or precancer compared with dermatologist diagnosis were assessed in screened patients 14 months before the intervention (February 18, 2014, through April 30, 2015) and after the intervention (June 18, 2015, through August 30, 2016).Among 258 patients offered screening (median age, 70 years; age range, 35-94 years; 255 [98.8%] male), 189 (73.3%) received CSE and 69 (26.7%) declined. A total of 62 of 189 patients (32.8%) were referred to a dermatologist after intervention: 33 (53.2%) for presumptive skin cancers and 15 (24.2%) for precancers. Nine of 50 patients (18.0%) evaluated in dermatology clinic underwent biopsy to exclude skin cancer. Correct diagnoses were made by PCPs in 13 of 38 patients (34.2%; 4 of 27 patients [14.8%] diagnosed with skin cancers and 5 of 11 patients [45.5%] diagnosed with actinic keratoses). Comparison of all outpatient visits for the 5 main participating PCPs before vs after intervention revealed no significant differences in dermatology referrals overall and those for presumptive skin cancer or actinic keratoses, skin biopsies, or PCP diagnostic accuracy with the exception of significantly fewer postintervention dermatology referrals that lacked specific diagnoses (25 [1.0%] vs 10 [0.4%], P = .01).This pilot study suggests that PCP-based skin cancer training and screening are feasible and have the potential to improve PCP diagnostic accuracy without increasing specialty referrals or skin biopsies. Additional studies comparing screening rates, specialty referrals, and patient outcomes in trained vs untrained PCPs are needed before screening is widely implemented in large health care systems in the United States.
View details for DOI 10.1001/jamadermatol.2017.1324
View details for PubMedID 28593242
Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities.
Response to programmed death 1 (PD-1) inhibitors has been associated with programmed death ligand 1 (PD-L1) expression levels in several cancers, but PD-L1 expression and its clinical significance in basal cell carcinoma (BCC) are unknown to date.To assess PD-L1 expression in treatment-naive and treated BCCs.This investigation was a cross-sectional study at a single academic tertiary referral center. Immunohistochemical staining on formalin-fixed BCCs from a dermatology clinic were examined in masked fashion by a dermatopathologist and a dermatologist. The study dates were March 31, 2014, to June 7, 2016.Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs.Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities.Among 138 BCCs from 62 patients (43 males and 19 females; mean [SD] age at biopsy, 61.6 [13.7] years), 89.9% (124 of 138) were positive for PD-L1 expression in tumor cells, and 94.9% (131 of 138) were positive for PD-L1 expression in TILs, defined as greater than 5% positive immunohistochemical staining in the respective cell populations. The PD-L1 immunohistochemical staining intensity of 78 treated BCCs compared with 60 treatment-naive BCCs was significantly different in tumor cells (32% vs 7%, P = .003) and TILs (47% vs 18%, P = .008) after adjusting for the age at diagnosis. In a multivariable model adjusting for age, sex, and BCC location, PD-L1 staining intensity in tumor cells increased with the number of distinct prior treatment modalities (median, 0.12; interquartile range, 0.03-0.20; P = .007).Our data suggest that PD-1 immunotherapy may have activity against BCCs, including in those that have been previously treated. This hypothesis needs to be tested in future clinical trials.
View details for DOI 10.1001/jamadermatol.2016.5062
View details for PubMedID 28259105
- Elder mistreatment training gaps among dermatology resident physicians and opportunity to improve care of a vulnerable population: A cross-sectional study. Journal of the American Academy of Dermatology 2017; 76 (2): 360-362
Initial in vitro functional characterization of serum exosomal microRNAs from patients with metastatic basal cell carcinoma
British Journal of Dermatology
2017; March: e187–e190
View details for DOI 10.1111/bjd.15508
Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma
2016; 152 (5): 527-532
Smoothened inhibitors (SIs) are a new type of targeted therapy for advanced basal cell carcinoma (BCC), and their long-term effects, such as increased risk of subsequent malignancy, are still being explored.To evaluate the risk of developing a non-BCC malignancy after SI exposure in patients with BCC.A case-control study at Stanford Medical Center, an academic hospital. Participants were higher-risk patients with BCC diagnosed from January 1, 1998, to December 31, 2014. The dates of the analysis were January 1 to November 1, 2015.The exposed participants (cases) comprised patients who had confirmed prior vismodegib treatment, and the nonexposed participants (controls) comprised patients who had never received any SI. Because vismodegib was the first approved SI, only patients exposed to this SI were included.Hazard ratio for non-BCC malignancies after vismodegib exposure, adjusting for covariates.The study cohort comprised 180 participants. Their mean (SD) age at BCC diagnosis was 56 (16) years, and 68.9% (n = 124) were male. Fifty-five cases were compared with 125 controls, accounting for age, sex, prior radiation therapy or cisplatin treatment, Charlson Comorbidity Index, clinical follow-up time, immunosuppression, and basal cell nevus syndrome status. Patients exposed to vismodegib had a hazard ratio of 6.37 (95% CI, 3.39-11.96; P < .001), indicating increased risk of developing a non-BCC malignancy. Most non-BCC malignancies were cutaneous squamous cell carcinomas, with a hazard ratio of 8.12 (95% CI, 3.89-16.97; P < .001), accounting for age and basal cell nevus syndrome status. There was no significant increase in other cancers.Increased risk for cutaneous squamous cell carcinomas after vismodegib therapy highlights the importance of continued skin surveillance after initiation of this therapy.
View details for DOI 10.1001/jamadermatol.2015.4330
View details for PubMedID 26914338
AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma.
2015; 12 (4): 599-609
The Hedgehog (Hh) pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK) is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.
View details for DOI 10.1016/j.celrep.2015.06.054
View details for PubMedID 26190112
A pilot study on mobile phones as a means to access maternal health education in eastern rural Uganda.
Journal of telemedicine and telecare
2015; 21 (1): 14-17
Maternal mortality in Uganda has remained relatively high since 2006. We studied access to mobile phones and people's interest in receiving audio-based maternal health lessons delivered via a toll-free telephone line. Interviews were conducted, using a male and a female translator, with 42 men and 41 women in four villages located in eastern rural Uganda. Most of the participants were recruited through systematic sampling, but some were recruited through community organizations and antenatal clinics. Ownership of a mobile phone was reported by 79% of men and by 42% of women. Among those who did not own a mobile phone, 67% of men and 88% of women reported regularly borrowing a mobile phone. Among women, 98% reported interest in receiving maternal mobile health lessons, and 100% of men. Providing local communities with mobile maternal health education offers a new potential method of reducing maternal mortality.
View details for DOI 10.1177/1357633X14545433
View details for PubMedID 25059242