First reported case of concurrent sonidegib and radiotherapy for recurrent, advanced basal cell carcinoma

Basal cell carcinoma (BCC ) is the most common human malignancy. Systemic therapy with a sonic hedgehog (SHH) pathway inhibitor plays an important role in the treatment of advanced BCC . Literature on concurrent use of radiation therapy (RT) with SHH inhibitors has been minimal and has solely been focused on vismodegib. We present a case report of a patient with recurrent basal cell carcinoma involving the high-risk area of the face, who was denied surgery due to comorbidities and difficulty in obtaining complete tumor removal without cosmetic or functional impairment. The patient received combined treatment of fractionated radiation with concurrent sonidegib and had complete clinical response with no significant toxicities. This is the first reported case on the use of concurrent RT with sonidegib for management of recurrent basal cell carcinoma of the head and neck

Direct innominate artery ostial cannulation using retrograde cardioplegia cannula in Type A dissection

Objective: Axillary and innominate artery (IA) cannulation using side graft has some limitations in patients having ascending aortic dissection (AAD) with flap extending in major neck vessels. We retrospectively analyzed the outcomes of a direct under vision innominate ostial cannulation strategy for antegrade cerebral perfusion (ACP) using a retrograde balloon-tip cardioplegia cannula. Patients and Methods: This was a retrospective analysis of all patients who were operated on for AAD with a dissection flap extending into major neck vessels between November 01, 2020 and November 30, 2022. Demographic data were noted, and comorbidities were listed. The kind of surgery patients underwent was noted: three patients underwent modified Bentall's procedure, five had to ascend aortic replacement, and one patient underwent David's procedure. All patients had open distal anastomosis using moderate hypothermia with ACP by direct under vision cannulation of the true lumen of the IA using a balloon-tip retrograde cardioplegia cannula. Intraoperative parameters such as cross-clamp time, cardiopulmonary bypass time, temperature range during circulatory arrest, and total operative time were noted. The primary outcome was a comparison of the incidence of stroke, seizures, and psychosis and the secondary outcome was an analysis of end-organ malperfusion, intensive care unit (ICU) stays, total hospital stay, and 30-day mortality. Results: We retrospectively analyzed the surgical data of nine patients who were operated on between November 01, 2020 and November 20, 2022 by this technique and found that the incidence of stroke, seizures organ malperfusion, ICU stay, and hospital stay was comparable to other techniques of ACP (axillary artery/direct IA cannulation), but the operative time was a less, and local complications due to axillary cannulation such as shoulder pain and upper limb weakness and seroma were not seen. Conclusion: Direct vision cannulation of the true lumen of the IA using a retrograde balloon-tip cannula is a cost-effective and time-saving method. It evades the limitations of well-established ACP techniques such as direct IA cannulation using Seldinger's technique which is a blind procedure and also has no local complications of the cannulating right axillary artery. Our results show that this procedure is less time-consuming and is noninferior to the other two methods of ACP in patients getting operated on for AAD with open distal anastomosis under moderate hypothermia. Further studies with a larger sample size are needed to validate this preliminary study

What Is the Status of Regenerative Therapy in Heart Failure?

Purpose of Review Heart failure remains a major public health concern with high burden of morbidity and mortality despite advances in pharmacotherapy, device therapy, and surgical and percutaneous techniques. Cardiac regeneration may have a role to play in these patients with a huge unmet need for these therapies in patients with chronic ischemic heart disease, post-infarct heart failure, dilated cardiomyopathy, and heart failure with preserved ejection fraction. Recent Findings In this review, we focus on the pre-clinical and translational basis for different modes of cardiac regenerative medicine and then critically appraise the clinical evidence amassed from pivotal clinical trials focused on cardiac regeneration for ischemic and non-ischemic cardiomyopathies. Cardiac regenerative medicine is rapidly evolving with novel approaches involving cell-based, cell-free, tissue engineering, and hybrid therapies to achieve myocardial regeneration and repair. Further studies are warranted with a robust comparison arm with optimal contemporary medical therapy to translate regenerative therapies to a clinical reality

Definitive single fraction stereotactic ablative radiotherapy for inoperable early-stage breast cancer: A case report

We review a case of inoperable early stage breast cancer treated definitively with the use of stereotactic ablative radiotherapy (SABR). A 57-year-old female with a history of decompensated cirrhosis with early stage breast cancer was treated with 25 Gy in one fraction. At her 7-month follow up visit, there was a complete resolution of disease on imaging. This case represents a novel approach for the treatment of breast cancer with SABR when surgery is contraindicated

The chromatin remodeling factor BRG1 stimulates nucleotide excision repair by facilitating recruitment of XPC to sites of DNA damage

BRG1 is a catalytic subunit of the human SWI/SNF-like BAF chromatin remodeling complexes. Recent findings have shown that inactivation of BRG1 sensitizes mammalian cells to various DNA damaging agents, including ultraviolet (UV) and ionizing radiation. However, it is unclear whether BRG1 facilitates nucleotide excision repair (NER). Here we show that re-expression of BRG1 in cells lacking endogenous BRG1 expression stimulates nucleotide excision repair of UV induced DNA damage. Using a micropore UV radiation technique, we demonstrate that recruitment of the DNA damage recognition protein XPC to sites of UV lesions is significantly disrupted when BRG1 is depleted. Chromatin immunoprecipitation of the endogenous DDB2 protein, which is involved in recruiting XPC to UV-induced CPDs (cyclobutane pyrimidine dimers), shows that elevated levels of BRG1 are associated with DDB2 in chromatin in response to UV radiation. Additionally, we detected slow BRG1 accumulation at sites of UV lesions. Our findings suggest that the chromatin remodeling factor BRG1 is recruited to sites of UV lesions to facilitate NER in human chromatin

Glottic Keratosis: Significance and Identification of Laryngoscopic Findings

Objective Glottic keratosis poses a challenge because a decision to biopsy must weigh the likelihood of dysplasia and cancer against the voice outcome after biopsy. We determined the significance of laryngoscopic findings and agreement among clinicians to identify those specific findings. Study Design Retrospective case-control study. Setting Tertiary care university hospital. Methods Adults with glottic keratosis with preoperative office laryngoscopies were included. Preoperative videostroboscopies were reviewed by a blinded reviewer. Multivariable logistic regression was used to examine the correlation between laryngoscopic appearance of glottic keratosis and presence or absence of high-grade dysplasia or carcinoma on biopsies. Consensus among head and neck cancer surgeons to detect specific laryngoscopic findings was evaluated by presenting representative laryngoscopies to a blinded cohort. Interrater reliability was calculated using Fleiss’s κ. Results Sixty glottic keratotic lesions met inclusion criteria. On logistic regression, both erythroplakia and aberrant microvasculature like vascular speckling were significantly associated with high-grade dysplasia and carcinoma, P = .002 and P = .03, respectively. Interrater reliability among clinicians to identify erythroplakia and aberrant microvasculature was minimal, κ = 0.35 and κ = 0.29, respectively. Interrater reliability was improved with the use of virtual chromoendoscopy. Conclusion The presence of erythroplakia and aberrant microvasculature in glottic keratosis is associated with the presence of high-grade dysplasia or carcinoma. Virtual chromoendoscopy can be used to improve reliability for detecting erythroplakia and vascular speckling, and this is a potential area for practice-based learning. Clinicians should identify and consider immediate diagnostic biopsy of suspicious glottic keratosis

Ebstein's Anomaly: "The One and a Half Ventricle Heart"

Abstract Objective: Ebstein's anomaly remains a relatively ignored disease. Lying in the 'No Man's land' between congenital and valve surgeons, it largely remains inadequately studied. We report our short-term results of treating it as a 'one and a half ventricle heart' and propose that the true tricuspid annulus (TTA) 'Z' score be used as an objective criterion for estimation of 'functional' right ventricle (RV). Methods: 22 consecutive patients undergoing surgery for Ebstein's anomaly were studied. Echocardiography was performed to assess the type and severity of the disease, tricuspid annular dimension and its 'Z' score. Patients were operated by a modification of the cone repair, with addition of annuloplasty, bidirectional cavopulmonary shunt (BCPS) and right reduction atrioplasty to provide a comprehensive repair. TTA 'Z' score was correlated later with postplication indexed residual RV volume. Results: There was one (4.5%) early and no late postoperative death. There was a significant reduction in tricuspid regurgitation grading (3.40±0.65 to 1.22±0.42, P2) is recommended. The short-term outcomes of our technique are promising