Intralesional human papillomavirus vaccine for the treatment of recalcitrant cutaneous warts.

Human papillomavirus (HPV) is ubiquitously distributed in the population worldwide and its most frequent clinical presentation is cutaneous warts. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional HPV 9-valent vaccine for the treatment of recalcitrant warts. A retrospective study was performed for all cases of cutaneous warts treated with intralesional 9-valent HPV vaccine between January 2017 and March 2021. Epidemiologic, clinical, and treatment data, including safety and effectiveness scores, were reviewed. Our cohort was composed of 20 patients: 13 adults and seven children. Twelve patients (60%) displayed a complete response whereas 8 patients (40%) showed a partial response. Older age was associated with a better response to treatment, while a history of laser therapy was associated with a worse prognosis. Adverse events were local, transient, and negligible. No systemic adverse effects were reported. Intralesional 9-valent HPV vaccine may be considered for the treatment of recalcitrant cutaneous warts. Controlled studies are required to confirm these results.

Monitoring oral propranolol for infantile hemangiomata.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5 mg/kg bid; 2 weeks later the dosage was escalated to 1 mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3 h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation.

Ex vivo organotypic cultures for synergistic therapy prioritization identify patient-specific responses to combined MEK and Src inhibition in colorectal cancer.

Translating preclinical studies to effective treatment protocols and identifying specific therapeutic responses in individuals with cancer is challenging. This may arise due to the complex genetic makeup of tumor cells and the impact of their multifaceted tumor microenvironment on drug response. To find new clinically relevant drug combinations for colorectal cancer (CRC), we prioritized the top five synergistic combinations from a large in vitro screen for ex vivo testing on 29 freshly resected human CRC tumors and found that only the combination of mitogen-activated protein kinase kinase (MEK) and proto-oncogene tyrosine-protein kinase Src (Src) inhibition was effective when tested ex vivo. Pretreatment phosphorylated Src (pSrc) was identified as a predictive biomarker for MEK and Src inhibition only in the absence of KRASG12 mutations. Overall, we demonstrate the potential of using ex vivo platforms to identify drug combinations and discover MEK and Src dual inhibition as an effective drug combination in a predefined subset of individuals with CRC.

Feasibility of hybrid Ivor-Lewis oesophagectomy after sleeve gastrectomy.

Oesophageal resection is a challenging procedure, and it is more so in patients who have undergone bariatric procedures, especially after laparoscopic sleeve gastrectomy. We present the case of a patient with a history of an laparoscopic sleeve gastrectomy who underwent a hybrid Ivor-Lewis oesophagectomy in which the sleeve was successfully used to reconstruct the upper gastrointestinal tract.

A review of combined treatments for melasma involving energy-based devices and proposed pathogenesis-oriented combinations.

BACKGROUND: Melasma is an acquired disorder of hyperpigmentation, affecting a million individuals worldwide. Energy-based devices (EBDs) employed to treat melasma include various types of lasers, intense pulsed light (IPL), and radiofrequency (RF). Recent studies have attempted to address recalcitrant and recurring melasma by combining energy-based devices with topical or oral medications. OBJECTIVE: This article reviews EBDs-based augmented treatment for melasma and suggests practical pathogenesis-oriented treatment regimens. Treatment algorithms are proposed to address various components of melasma. METHODS: A systematic PubMed search was conducted acquiring information from various studies on combination treatments of melasma involving EBDs. RESULTS: The 286 retrieved articles were filtered by title to contain at least one type of energy-based modality such as laser, IPL, or RF along with at least one other treatment method. Based on their subject matter, combinations were further categorized into the subheadings: laser plus medication, laser plus laser, and IPL- and RF-containing treatment methods. CONCLUSION: There are many energy-based combination treatments that have been explored for mitigation of melasma including laser therapy with medication, multi-laser therapies, IPL, RF, and microneedling devices. Melasma is an exceedingly difficult condition to treat, however, choosing the appropriate tailor-made treatment combination can improve the final outcome.

Major pulmonary resection after neoadjuvant chemotherapy or chemoradiation in potentially resectable stage III non-small cell lung carcinoma.

The aim of this study was to identify predictors of postoperative outcome and survival of locally advanced non-small cell lung carcinoma (NSCLC) resections after neoadjuvant chemotherapy or chemoradiation. Medical records of all patients with clinical stage III potentially resectable NSCLC initially treated by neoadjuvant chemotherapy or chemoradiation followed by major pulmonary resections were retrieved from the databases of four Israeli Medical Centers between 1999 to 2019. The 124 suitable patients included, 86 males (69.4%) and 38 females (30.6%), with an average age of 64.2 years (range 37-82) and an average hospital stay of 12.6 days (range 5-123). Complete resection was achieved in 92.7% of the patients, while complete pathologic response was achieved in 35.5%. The overall readmission rate was 16.1%. The overall 5-year survival rate was 47.9%. One patient (0.8%) had local recurrence. Postoperative complications were reported in 49.2% of the patients, mainly atrial fibrillation (15.9%) and pneumonia (13.7%), empyema (10.3%), and early bronchopleural fistula (7.3%). The early in-hospital mortality rate was 6.5%, and the 6-month mortality rate was 5.6%. Pre-neoadjuvant bulky mediastinal disease (lymph nodes > 20 mm) (p = 0.034), persistent postoperative N2 disease (p = 0.016), R1 resection (p = 0.027), preoperative N2 multistation disease (p = 0.053) and postoperative stage IIIA (p = 0.001) emerged as negative predictive factors for survival. Our findings demonstrate that neoadjuvant chemotherapy or chemoradiation in locally advanced potentially resectable NSCLC, followed by major pulmonary resection, is a beneficial approach in selected cases.

Semi-prone position for thoracoscopic resection of a rare oesophageal tumour.

Oesophageal schwannomas are extremely rare tumours arising from Schwann cells of the neural sheath, with less than 115 cases reported in the English literature. These tumours are usually sporadic and account for about 2% of all stromal oesophageal tumours. Diagnosis is usually confirmed by the presence of positive immunohistochemical marker S-100 and absence of CD117, CD34, smooth muscle actine and Desmin. Treatment can vary from enucleation to oesophagectomy. Herein, we report a case of a 61-year-old woman who presented with progressive dysphagia. Computerized tomography scan revealed a 5 × 3 cm mass extending proximal to the azygos arch. Oesophagogastroduodenoscopy showed a submucosal mass at 20-24 cm from the incisors. Endoscopic ultrasound showed a 6 × 3 cm well-circumscribed mass originating from the fourth layer, suspicious for a gastrointestinal stromal tumour. The patient underwent thoracoscopic enucleation of the tumour in a semi-prone position. Final pathology was consistent with a completely resected benign oesophageal schwannoma, positive for S-100.

Moisture Response Films Versus the Starch Iodine Test for the Detection of Palmar Hyperhidrosis.

BACKGROUND: The starch iodine test (SIT) is the gold-standard diagnostic tool for primary palmar hyperhidrosis (PPH). OBJECTIVE: This study aimed to evaluate the clinical effectiveness and safety profile of a novel approach for the detection of PPH by moisture response films (MRF) in comparison to the SIT. METHODS: This prospective comparative study of the 2 tests was conducted on 17 patients with PPH. Disease severity was evaluated by the SIT and the MRF methods during 4 sessions (twice before and twice after botulinum toxin [BTX] injections) on different days and by different investigators. The physician's global assessment (PGA) scoring of the comparable visual results was evaluated by 2 blinded independent dermatologists. The Hyperhidrosis Disease Severity Scale (HDSS) scores of the patients at baseline and after the BTX injections were correlated with the SIT and MRF results. RESULTS: The objective PGA scoring of the SIT results demonstrated poor correlation, whereas the objective PGA scoring of the MRF results correlated highly with the patients' HDSS scores both at baseline and after the BTX injections. CONCLUSION: Analysis of palmar hyperhidrosis by means of MRF was superior to SIT and was demonstrated to be more efficient, convenient, and accurate.

Negative-Pressure Vacuum Therapy for High-Output Chyle Leak Following Neck Dissection.

Chyle fistula is a challenging complication following neck dissection carrying a high morbidity and mortality rate. Herein we present a challenging case of successful management of high-output left-sided cervical chyle fistula with negative-pressure vacuum (VAC) therapy in a case where all conservative treatments failed. A 40-year-old man with lymphoma and supraglottic carcinoma underwent endoscopic resection and bilateral neck dissections. He developed high-output chyle fistula, nonresponsive to conservative treatments. Double-layered Vicryl mesh was placed between the sponge and the jugular vein to prevent vascular injury. Immediately after initiation of the VAC therapy, the output decreased, and completely stopped after 3 days. The VAC therapy was continued for additional 5 days to ensure complete seal of the fistula by granulation tissue, by which time the wound was primarily closed. VAC therapy seems to be a safe and effective treatment for high-output cervical chyle fistula following neck dissection, avoiding complex surgical interventions. Thoracic surgeons should be aware of this low-morbidity and potentially effective treatment modality for this challenging complication.

Enhanced Percutaneous Delivery of Beta-Blockers Using Thermal Resurfacing Drug Delivery System for Topical Treatment of Infantile Hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are the most common vascular tumors in children. In the past few years, topical beta-blockers (bBs) have been reported to be an effective treatment of superficial IHs. OBJECTIVE: We sought to evaluate the clinical effectiveness and safety profile of enhanced percutaneous delivery of bBs for the treatment of IH. METHODS: A retrospective study of all cases of IHs treated with enhanced percutaneous delivery of bBs between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. RESULTS: The study included 11 patients with a total of 11 IHs. Of the total number of IHs, 7 (63.7%) showed a good response to treatment and 4 (36.3%) had a partial response; thus all patients (100%) had good or partial response to treatment. No systemic or local adverse effects were reported. LIMITATIONS: This is an uncontrolled retrospective study. CONCLUSION: Enhanced percutaneous delivery of bBs is a safe and efficient topical therapy for IH.

A Potentially Malignant Giant Esophageal Paraganglioma.

Paragangliomas are rare neuroendocrine tumors derived from extraadrenal autonomic paraganglia, which may secrete catecholamines. They are potentially metastatic and require very long-term follow-up. Esophageal paragangliomas are extremely rare and present a diagnostic challenge. Lack of clinical suspicion and unrecognized catecholamine hypersecretion may lead to hemodynamic instabilities during surgery. Two patients with esophageal paragangliomas were previously reported. We report a 39-year-old man with a giant high-risk esophageal paraganglioma who underwent a hybrid minimally invasive 3-hole esophagectomy.

Efficacy of a combination of diluted calcium hydroxylapatite-based filler and an energy-based device for the treatment of facial atrophic acne scars.

BACKGROUND: Treatment options for atrophic acne scars include the use of various energy-based devices (EBDs) and dermal fillers. AIM: To evaluate the level of improvement and safety of four treatments for atrophic acne scars used in our centre. METHODS: We reviewed the medical records of all patients with acne scars treated between 2013 and 2016 with one of four treatments: ablative fractional CO2 laser (FACL), a radiofrequency (RF) bipolar device, a 1540 nm nonablative fractional laser (NAFL) and injection of diluted calcium hydroxylapatite (CaHA). The EBDs were used either as monotherapy or in combination with diluted CaHA. The aesthetic improvement achieved following the various treatments was evaluated by the patients and by two independent dermatologists who were not involved in the treatments. The patients also rated their satisfaction with the treatment, recorded the number of days of downtime (including time to full recovery and time for resolution of redness) and reported any adverse effects (AEs). RESULTS: In total, 352 patients (mean ± SD age 28.7 ± 8.7 years; 65.6% women, 34.4% men) were treated for acne scars. The integrated mean Global Assessment Scale by both dermatologists and patients were highest for the combined CaHA-FACL treatment at separate sessions (injection in one session; laser treatment in another) (P < 0.001). However, patients treated with FACL reported more AEs and longer downtime and duration of erythema. CONCLUSION: The combination of a diluted CaHA-based filler injection followed by FACL in separate treatment sessions yielded better aesthetic improvement compared with the other tested treatments.

Anterior Scleritis Associated with Pemphigus Vulgaris.

We present a rare co-occurrence of anterior scleritis developing in a patient with recalcitrant pemphigus vulgaris. We discuss the clinical and therapeutic implications of these two conditions and offer concise recommendations.

Direct and cytokine-mediated effects of albumin-fused growth hormone, TV-1106, on CYP enzyme expression in human hepatocytes in vitro.

Some biologics can modulate cytokines that may lead to changes in expression of drug-metabolizing enzymes and cause drug-drug interactions (DDI). DDI potential of TV-1106-an albumin-fused growth hormone (GH)-was investigated. In this study, human blood was exposed to recombinant human growth hormone (rhGH) or TV-1106, followed by isolation of the plasma and its application to human hepatocytes. While the treatment of blood with rhGH increased multiple cytokines, treatment of blood with TV-1106 had no effect on any of the nine cytokines tested. The interleukin (IL)-6 concentration was higher in the rhGH then in the TV-1106-treated plasma (P < .05). While rhGH had little or no effect on CYP1A2 or CYP2C19 mRNA but increased CYP3A4 mRNA twofold, TV-1106 had little or no effect on cytochrome P450 (CYP) mRNAs in hepatocytes. Although the plasma from rhGH-treated blood lowered CYP1A2 activity, the TV-1106 plasma had no effect on CYP activities. The CYP1A2 activity was lower in the rhGH- then in the TV-1106-plasma treated hepatocytes (P < .05). The results indicated that fusing GH with albumin made TV-1106 an unlikely participant of CYP1A2, CYP2C19 or CYP3A4-facilitated, direct or cytokine-driven DDI.

Prevalence of choroidal nevus and retinal pigment epithelial alterations in vitiligo patients.

PURPOSE: To investigate ocular manifestations in patients with vitiligo by multimodal imaging, including optical coherence tomography (OCT), color fundus photography, and fundus autofluorescence (FAF). METHODS: In this prospective, observational clinical study, vitiligo patients underwent ophthalmologic and dermatologic clinical assessment and imaging by spectral-domain OCT, FAF, and color fundus imaging. Ocular echography was performed as indicated. Statistical analysis was performed using paired T test and Pearson correlation. RESULTS: A total of 61 eyes of 31 vitiligo patients were examined. Ocular findings consisted of choroidal nevi (n = 10, 32%), of which four (40%) were bilateral; two patients (6.5%) had a prominent choroidal pattern, two (6.5%) had hypopigmentary retinal pigment epithelium (RPE) lesions, and one (3.2%) had peripapillary atrophy of the RPE. Choroidal nevi were demonstrated only in eyes of patients with generalized vitiligo and were more common with upper body involvement (p = 0.02) and more prevalent in women (p = 0.02). Hypopigmentary lesions were detected in two patients and demonstrated on OCT as RPE atrophy and as photoreceptor/RPE changes. CONCLUSIONS: In this case series, vitiligo patients had a higher rate of choroidal nevi than previously reported. The hypopigmentary vitiliginous fundus lesions were depicted on OCT as photoreceptor and RPE atrophy. These findings may suggest the advisability of regular ocular monitoring for vitiligo patients.

Compositional differences between Copaxone and Glatopa are reflected in altered immunomodulation ex vivo in a mouse model.

Copaxone (glatiramer acetate, GA), a structurally and compositionally complex polypeptide nonbiological drug, is an effective treatment for multiple sclerosis, with a well-established favorable safety profile. The short antigenic polypeptide sequences comprising therapeutically active epitopes in GA cannot be deciphered with state-of-the-art methods; and GA has no measurable pharmacokinetic profile and no validated pharmacodynamic markers. The study reported herein describes the use of orthogonal standard and high-resolution physicochemical and biological tests to characterize GA and a U.S. Food and Drug Administration-approved generic version of GA, Glatopa (USA-FoGA). While similarities were observed with low-resolution or destructive tests, differences between GA and USA-FoGA were measured with high-resolution methods applied to an intact mixture, including variations in surface charge and a unique, high-molecular-weight, hydrophobic polypeptide population observed only in some USA-FoGA lots. Consistent with published reports that modifications in physicochemical attributes alter immune-related processes, genome-wide expression profiles of ex vivo activated splenocytes from mice immunized with either GA or USA-FoGA showed that 7-11% of modulated genes were differentially expressed and enriched for immune-related pathways. Thus, differences between USA-FoGA and GA may include variations in antigenic epitopes that differentially activate immune responses. We propose that the assays reported herein should be considered during the regulatory assessment process for nonbiological complex drugs such as GA.

Paraneoplastic pityriasis rubra pilaris: case report and literature review.

Pityriasis rubra pilaris (PRP; MIM 173200) is an uncommon papulosquamous inflammatory dermatosis. Only a few cases of PRP associated with an underlying malignancy have been documented. We investigated a 59-year-old patient presenting with a fulminant form of PRP recalcitrant to systemic retinoid therapy, in whom the skin disease heralded a diagnosis of cholangiocarcinoma. We searched the MEDLINE database to find articles reporting on similar associations of PRP with malignancies. We identified 10 studies linking PRP and malignancies, but an association between PRP and cholangiocarcinoma has not yet been reported.

Lobectomy for Non-Small Cell Lung Cancer after Coronary Artery Bypass Grafting Surgery.

BACKGROUND: The efficacy of video-assisted thoracoscopic surgery lobectomy in patients with previous coronary artery bypass grafting (CABG) surgery is controversial. OBJECTIVES: To investigate whether skeletonized left internal mammary artery (LIMA) mobilization contributes to the development of severe adhesions, which will affect what type of lung surgery (open or closed procedure) will be required in the future. METHODS: Eight patients (mean age 73.9 years) with previous CABG surgery using a LIMA to left anterior descending (LAD) graft underwent left-sided lobectomy for operable non-small cell lung carcinoma. RESULTS: The lobectomy by thoracotomy rate was 62.5% (5 patients), generally in patients with tumors in the left upper lobe or in patients post-neoadjuvant chemotherapy, while the video-assisted thoracic surgery lobectomy rate was 37.5% (3 patients). Mean hospital stay was 8.3 days. There was no mortality or major morbidity, apart from six minor complications in four patients (50%) (air leak, atrial fibrillation, atelectasis, pneumonia). CONCLUSIONS: Patients with operable non-small cell lung carcinoma following CABG surgery who need left upper lobe resection do not benefit from the video-assisted thoracoscopic surgery technique due to significant adhesions between the LIMA to LAD graft and the lung. The method of preserving a small portion of the lung on the LIMA to LAD graft may help during left upper lobe resections. Adhesions in the left pleural space after LIMA mobilization appear to minimally affect left lower lobe video-assisted thoracoscopic surgery.