FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint inhibitors for the Treatment of Biliary Tract Cancer.

On September 2, 2022, the Food and Drug Administration (FDA) approved durvalumab in combination with cisplatin and gemcitabine, for the treatment of patients with unresectable or metastatic biliary tract cancers (BTC). On October 31, 2023, the FDA approved pembrolizumab in combination with cisplatin and gemcitabine for the same indication. Approvals were based on two randomized, multiregional, placebo-controlled trials, which randomly allocated patients to receive durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966) in combination with chemotherapy or placebo in combination with chemotherapy. Overall survival (OS) was the primary endpoint in both studies. In both studies, a statistically significant and clinically meaningful improvement in OS was demonstrated. In the TOPAZ-1 trial the median OS of patients receiving durvalumab was 12.8 months (95% confidence interval [CI] 11.1, 14.0) and 11.5 months (95% CI 10.1, 12.5) in patients receiving placebo (HR 0.80 [95% CI 0.66, 0.97]). In the KEYNOTE-966 trial, the median OS of patients receiving pembrolizumab was 12.7 months (95% CI 11.5, 13.6) and 10.9 months (95% CI 9.9, 11.6) in patients receiving placebo (HR 0.83 [95% CI 0.72, 0.95]). The addition of checkpoint inhibitors to standard of care chemotherapy for this indication did not reveal any new adverse event signals and the safety profile was generally consistent with the known clinical experience with durvalumab, pembrolizumab, and the backbone chemotherapy regimen. The approvals of durvalumab and pembrolizumab in combination with standard of care cisplatin and gemcitabine for the treatment of unresectable or metastatic BTC add two new therapeutic option for these patients.

Landscape Analysis of Generic Availability for Oncologic Drugs.

BACKGROUND: Improving generic drug development in oncology is a key long-term goal in providing safe, effective, and affordable care to patients with a diagnosis of cancer in the United States. There are multiple drug and non-drug related variables that may influence generic drug development. To illustrate pertinent associations relevant to generic drug competition in oncology, our study assessed variables that have potentially led to difference in generic competition as compared to drug products in other therapeutic areas, i.e., cardiovascular disease in this case. METHODS: Using a combination of FDA and publicly available data, we categorized individual drug approvals from 1950 to 2021 with either an oncology or cardiovascular indication. Descriptive statistics highlighted the timeline of approval as stratified by indications. Machine learning methodology was used to assess variables associated with abbreviated new drug application (ANDA) availabilities (i.e., generic drug availabilities). Kaplan-Meier analysis with log-rank test compared the difference in the time to approval of first ANDA among products that were off-patent at the time of analysis. A multivariable Cox proportional hazards model with forward selection was used to identify variables (e.g., regulatory recommendation issued, dosage form) that were associated with ANDA availability among products that were off-patent. RESULTS: 434 separate reference listed drugs (RLDs) with varying strengths were identified, 212 (49%) for oncology and 222 (51%) for cardiovascular indications. Compared with cardiovascular products, a greater proportion of RLDs with an oncology indication were approved after 2000 (61% vs. 34%). Also, a smaller proportion of oncologic products had generics (49% vs. 80%). Machine learning methodology revealed RLD age, patent status, product complexity, sales/prescriptions, and regulatory recommendations as variables that were associated with generic availability. Among products off-patent at the time of analysis, the median time from RLD approval to the first ANDA approval was longer for oncologic products compared to cardiovascular products (15.4 years (95% CI 13.8, 17.9) versus 12.3 years (95% CI 10.7, 13.5), p = 0.008). Cox regression analyses identified the variables of product dosage form and regulatory recommendation of requiring patient enrollment for bioequivalence (BE) establishment as being associated with reduced likelihood of ANDA approval for oncologic drugs. CONCLUSION: Oncology indications were found to have a longer time from RLD approval to first ANDA approval compared with cardiovascular drugs. Our work has identified variables that may influence time to ANDA availability, with the requirement of patient enrollment for BE assessment as one important opportunity for future stakeholder engagement and regulatory considerations.

Patterns and Trends of Facial Fractures at a Tertiary Care Trauma Center in India - A 13 years Retrospective Study.

Study Design: Retrospective study. Objective: The purpose of this study was to retrospectively analyze the prevalence, pattern, diagnosis, and treatment of the facial fractures falling under ambit of facial plastic surgery in a multi-specialty hospital at India from the year 2006-2019. Methods: This retrospective study analyzed 1508 patients, having orbital fractures (from 2006 to 2019) for demographic data, cause of trauma, type of fracture, and the treatment given. The data were compiled in excel and analyzed by using SPSS version 21.0. Results: Out of these 1508 patient (1127 (74.73%)-males and 381 (25.27%)-females), the etiology of injuries was Road traffic accident (RTA) (49.20%), assault (26.52%), and sports injuries (11.47%). The most common fracture pattern was Isolated Orbit and/or Orbital Floor fracture in 451 patients (32.08%), followed by Mid-facial fractures (21.93%). Also, 105 patients (6.96%) experienced ocular/retinal trauma along with other fractures. Conclusions: Orbit, peri-ocular, and mid-face trauma comprised a large position of this study. It requires a great deal of expertise to treat such complex trauma, which is not covered in one specialty alone. Hence, a holistic approach of craniofacial fracture management, rather than limiting these skills to water-tight craniofacial compartments becomes necessary. The study highlights the critical need of multidisciplinary approach for predictable and successful management of such complex cases.

Waldenström macroglobulinemia with secondary pure red cell aplasia in a patient with metastatic castrate resistant prostate cancer receiving an immune checkpoint inhibitor: a case report.

BACKGROUND: Hypoproliferative anemia is a frequently encountered adverse event in cancer patients receiving immune checkpoint inhibitors (ICI). Secondary pure red cell aplasia (PRCA) is a rare but recognized immune related adverse event. With the burgeoning use of ICIs, the association of secondary PRCA with an underlying lymphoproliferative disorder is often overlooked. CASE PRESENTATION: We report a case of a 67-year-old non-Hispanic Caucasian male with metastatic castrate resistant prostate cancer, who developed severe transfusion dependent anemia with reticulocytopenia while receiving treatment with olaparib and pembrolizumab. His bone marrow findings demonstrated erythroid hypoplasia, in addition to a CD5-negative, CD10-negative monotypic B-cell population and a somatic MYD88L265P mutation. With a presence of an IgM-paraprotein, he was diagnosed with Waldenström macroglobulinemia (WM) with secondary PRCA and treated with 6 cycles of bendamustine and rituximab. He achieved a complete response with this regimen and was transfusion independent. CONCLUSION: In this case, underlying WM was uncovered through systematic investigation of anemia caused by ICI therapy. This report highlights the possibility of a lymphoproliferative disorder in patients with concerns for PRCA with prior ICI exposure. If identified, treating the underlying lymphoproliferative disorder is highly efficacious in the management of the secondary PRCA.

Evolution and Trends of Facial Plastic Surgery and Facial Aesthetic Procedures in India: From Awakening to Revival.

Facial aesthetic surgery is an emerging branch worldwide. India, a torchbearer country in facial plastic surgery, has seen tremendous growth in medical technology, resources, and clientele over the past century. This study aims to study past practices and current trends in facial plastic surgery and aesthetic procedures in India by individually addressing commonly performed nonsurgical procedures (Botox, Kybella [Allergan, Irvine, CA], fillers, threads, micro-focused ultrasound, and nonsurgical hair restoration), and surgical procedures (rhinoplasty, blepharoplasty, hair transplant, and facelift). It also aims to further elaborate on the scope of facial aesthetics and make recommendations on prospects in the field. A structured scoping review and a subsequent evidence-based synthesis were done following an extensive literature search on various databases such as PubMed (National Institutes of Health, Bethesda, MD), LILACS (Latin American and Caribbean Center on Health Sciences Information, São Paulo, Brazil), MEDLINE (National Library of Medicine, Bethesda, MD), EMBASE (Elsevier, Amsterdam, the Netherlands), and Cochrane (Wiley, Hoboken, NJ). The initial search yielded 703 articles, out of which 20 were found to be relevant to the present study and discussed. It was found that there is an upward trend in the growth of facial plastic surgery in India, and a gradual shift in patient attitude toward nonsurgical aesthetic procedures was seen. This article affirms the growth of facial aesthetic surgery in India by highlighting the recent development and trends in the practices of surgeons. It also addresses the shortcomings in the current administration and makes recommendations to fill the existing loopholes in plastic surgery.

Effectiveness of HIFU Therapy for Nonsurgical Facial and Body Contouring: A Systematic Review of Prospective and Experimental Studies.

BACKGROUND: Liposuction, the most common body sculpting surgical procedure known today is associated with the risk of numerous complications. A safer and more noninvasive approach involves the use of high-intensity focused ultrasonography (HIFU) lasers, which work by selectively damaging fat tissue through apoptosis or necrosis induction of fat cells. The authors' systematic review was designed to identify the effectiveness of HIFU for nonsurgical facial and body contouring. METHODS: An exhaustive literature search was conducted of the PubMed/MEDLINE, Cochrane Central, Scopus, and EBSCO electronic databases for the period from November of 2005 to July of 2020. The full text of selected articles was reviewed for possible study inclusion, and articles fulfilling the inclusion criteria were recruited. Characteristics of the included studies were noted, and outcomes were assessed. Assessment of quality and risk of bias was performed for all the studies using the RevMan tool and the methodological index for nonrandomized studies. RESULTS: The initial search revealed a total of 4584 citations, of which only 11 were included in the present review: nine used HIFU for recontouring of the abdomen and only two used HIFU over the face and neck. Studies evaluated either the efficacy of HIFU or the safety of its use. The average total energy ranged from 140 to 248 J/cm 2 for the abdominal region and 0.3 to 1.2 J/cm 2 for the face and neck. The focal depth ranged from 1.1 to 1.8 cm. All the studies showed promising results with the use of HIFU. CONCLUSION: HIFU therapy is safe, effective, and minimally invasive, with predictable results when used for body and facial recontouring.

FDA Approval Summary: Ripretinib for Advanced Gastrointestinal Stromal Tumor.

On May 15, 2020, the FDA approved ripretinib for adult patients with advanced gastrointestinal stromal tumor who have received prior treatment with three or more kinase inhibitors, including imatinib. The approval was based on results from INVICTUS (NCT03353753), an international, multi-center, double-blind, placebo-controlled trial. Patients were randomly allocated (2:1) to receive either ripretinib 150 mg once daily (n = 85) or matching placebo (n = 44). The trial demonstrated a statistically significant improvement in progression-free survival (PFS) as assessed by modified RECIST v1.1 by blinded independent central review for patients randomized to ripretinib, with a median PFS of 6.3 months [95% confidence interval (CI): 4.6-6.9] compared with 1.0 month (95% CI: 0.9-1.7) for placebo [HR: 0.15 (95% CI: 0.09-0.25); P < 0.0001, stratified log-rank test]. There was no statistically significant difference in objective response rate in the ripretinib arm, 9% (95% CI: 4.2-18) compared with placebo 0% [(95% CI: 0-8); P = 0.0504, Fisher exact test]. The median overall survival (OS) in the ripretinib arm was 15.1 months (95% CI: 12.3-15.1) compared with 6.6 months (95% CI: 4.1-11.6) in the placebo arm. A formal statistical comparison of OS was not made due to the prespecified hierarchical analysis plan. The most common (≥20%) adverse events with ripretinib, in order of decreasing frequency, were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia, and vomiting. Other important risks of ripretinib include new primary cutaneous malignancies, hypertension, and cardiac dysfunction.

Cost-effectiveness of the Flapless Insertion of Zygomatic Implants Using Dynamic Navigation - A Retrospective Study.

Introduction: Zygomatic implants are an effective solution for rehabilitation of edentulous atrophic maxillae. However, the conventional technique of zygomatic implant placement is invasive, requires a longer healing period and is economically cumbersome. Therefore, the flapless technique of insertion of zygomatic implants using dynamic navigation system has been introduced. This study aims to compare the cost-effectiveness of flapless insertion of zygomatic implants using dynamic navigation to the conventional flap technique. Materials and Methods: The study participants were divided into two groups: Group A (n = 20) included patients treated by flapless insertion of zygomatic implants using dynamic navigation and Group B (n = 20) included patients treated with zygomatic implants using the flap technique. An analysis of the effectiveness of the implants was done using the concept of quality-adjusted prosthesis years, and an analysis of the costs was done by evaluating the treatment costs at each step. The data were collected, and analysis was done using IBM SPSS software. The Kruskal-Wallis rank-sum test was employed to analyse variations in costs and effects between the two groups. Results: The study showed that the distribution of costs varies across both the categories of the procedure. Group B shows lesser cost-effectiveness as compared to Group A. Conclusion: The technique of flapless insertion of zygomatic implants is cost-effective. However, further studies considering factors such as time and cost of productivity evaluating the cost-effectiveness should be conducted.

Interest of Oral and Maxillofacial Surgeons Towards Specialised Training in Facial Aesthetic and Plastic Surgery in India - An Evaluative Study.

Introduction: The Dental Council of India has included facial plastic surgery in the scope of practice of Oral and Maxillofacial Surgeons (OMFSs) in India. However, the knowledge and interests of these specialists towards facial plastic surgery are unexplored. Materials and Methods: A descriptive cross-sectional study consisting of a structured questionnaire tool with six domains and 46 questions was circulated amongst registered OMFSs in India. The study consisted of 950 participants. The data obtained from this questionnaire were coded and entered into Statistical Package for Social Sciences (SPSS) and a descriptive analysis was conducted. Results: The study yielded that only 33% of the participants were completely aware of facial fillers and 30.5% were aware of Botox procedure. However, there was complete awareness of blepharoplasty in 42%, cheiloplasty/palatoplasty in 65.8%, laser facial resurfacing in 23.7% and facial rejuvenation in 23.5% of the participants. Discussion: It was found that a high number of OMFSs felt that their exposure to plastic surgery during their post-graduation years was not sufficient.

Multidimensional Indicators as Enablers on Perception of Facial Beauty and Appearance among Indian Population: A Descriptive Cross-Sectional Study.

Background: Facial appearance has been a flagbearer of "beauty" since time immemorial. Perception of beauty is highly influenced by cultural, interpersonal, and intra-personal variations. Objectives: This study aimed to assess the perception of facial beauty and appearance through multidimensional influencing indicators among the Indian population, and to determine whether the physically attractive person possesses more personal and socially desirable traits than the comparatively less attractive individual. Materials and Methods: A study population of 474 with equal male and female population of Indian origin was selected. Their perception was assessed based on the prevalidated, self-administered questionnaire using a tool with five major multidimensional indicators. Six images were selected, three each of male and female subjects, and labeled as A, B, and C, in descending order of attractiveness. The multidimensional influencing indicator tool was self-administered to the participants and the responses were recorded individually. Results: Photograph A scored the highest out of the three grading scales in both males and females. Conclusion: The most attractive photograph, in both males and females, was deemed to be associated with higher scores of attractiveness and success.

Temporal Changes in Treatment Patterns for Rural and Urban Patients With Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND Our objectives were to evaluate geographic access to lung cancer treatment modalities in North Carolina and to characterize how practice patterns are changing over time. We hypothesized that rural patients would be less likely to undergo treatment compared to urban patients, with widening disparities over time.METHODS We identified patients with Stage I non-small cell lung cancer (NSCLC) from 2006 to 2015 using the North Carolina Central Cancer Registry linked with Medicaid, Medicare, and private insurance claims. The primary outcome was first-course treatment: surgery, radiation, or no treatment. Calendar years were split into earlier (2006-2010) and later (2011-2015) periods. We estimated the adjusted odds ratio (OR) of rural/urban status and time period with 1) surgery and 2) any treatment (surgery or radiation) using multivariable logistic regression.RESULTS Among 5504 patients, 3206 (58%) underwent surgery as initial therapy, 1309 (24%) received radiation as initial therapy, and 989 (18%) had no therapy. There were no rural-urban disparities in treatment patterns. For rural and urban patients, the odds of surgery decreased over time and the odds of radiation increased. We also found that only 48% of those receiving no treatment ever reached a surgeon or radiation oncologist.LIMITATIONS This was an insured, single-state population. Treatment preferences are unknown.CONCLUSIONS Among all treated patients, whether urban or rural, there was increasing use of radiation and decreasing use of surgery over time. Many patients without treatment never had a consultation with a surgeon/radiation oncologist, and this is an actionable target for improving treatment access for early-stage NSCLC.

Safety and Efficacy of Pembrolizumab Prior to Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia.

Programmed death 1 (PD-1) is an integral component of acute myelogenous leukemia (AML) immune evasion, chemotherapy resistance, and disease progression. PD-1 inhibitors are being investigated as treatment for AML in combination with hypomethylating agents and cytotoxic chemotherapy with encouraging findings. Although allogeneic stem cell transplantation (alloSCT) remains the most established curative treatment for patients with relapsed and refractory AML in complete remission, there are limited data on the clinical outcomes and safety of immune checkpoint inhibitors (ICIs) prior to alloSCT in AML. In the present study, we compared clinical outcomes of 9 patients with AML receiving high-dose cytarabine followed by pembrolizumab in a phase II clinical trial (NCT02768792) prior to alloSCT versus a historical control group of 18 AML patients who underwent alloSCT without prior ICI exposure. The nonparametric Jonckheere-Terpstra test was used to test for a difference in the ordered severity categories of acute graft-versus-host disease (GVHD) within 100 days of transplantation. Time-to-event estimates for overall survival and relapse-free survival were calculated using the Kaplan-Meier method and compared using a log-rank test. One-year survival was not significantly different between the treatment groups (67% versus 78%; P = .34). 100-day mortality was 0% in the ICI group versus 17% in the control group, and there was no increase in grade III-IV acute GVHD in patients treated with pembrolizumab prior to alloSCT. No chronic GVHD was seen in patients treated with pembrolizumab prior to alloSCT and who received post-transplantation cyclophosphamide (PTCy) as part of their conditioning regimen. These findings reinforce the safety and feasibility of ICI therapy prior to alloSCT in patients with AML, and suggest that PTCy may abrogate GVHD risk and severity in patients who receive ICI prior to undergoing alloSCT for AML.

Innovative approach for tear trough deformity correction using higher G prime fillers for safe, efficacious, and long-lasting results: A prospective interventional study.

BACKGROUND: One of the most challenging areas for facial rejuvenation is the lower eyelid. Apart from the protruding orbital fat causing lower lid bags, a discrete entity called the "tear trough deformity" is distinguishable in this area. AIM: The objective of this study is to compare and evaluate the standard technique of tear trough deformity correction with the lateral injection technique using a high G prime filler to establish a guideline for the safe and effective correction of tear trough deformity. METHODS: A prospective, double-blind, study was carried out from Dec 2017 to 2019 including 30 participants in the age range of 35-60 years. The participants were divided into two groups of 15 patients each. In group A patients, conventional technique with a low G Prime filler was used, whereas in group B, lateral injection technique with a high G Prime filler was used. RESULTS: Marked improvement was seen in appearance and skin quality on both the sides in all the patients. As compared to our technique (lateral injections) where a mean of 0.5 ml of filler was used to lift the cheek and reduce the tear trough, the standard technique (Mauricio de Maio's 3-point tear trough reshape technique) required a mean of 1.2 ml of filler for the same. Post-procedure complications including bruising and Tyndall effect were much higher (statistically significant) using the standard medial technique for the correction tear trough. CONCLUSION: Aesthetically satisfying results for the tear trough correction are possible, without actually injecting the tear trough directly, based on the knowledge of the underlying anatomy.

The CoVID-TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID-19.

BACKGROUND: Hospitalized patients with COVID-19 have increased risks of venous (VTE) and arterial thromboembolism (ATE). Active cancer diagnosis and treatment are well-known risk factors; however, a risk assessment model (RAM) for VTE in patients with both cancer and COVID-19 is lacking. OBJECTIVES: To assess the incidence of and risk factors for thrombosis in hospitalized patients with cancer and COVID-19. METHODS: Among patients with cancer in the COVID-19 and Cancer Consortium registry (CCC19) cohort study, we assessed the incidence of VTE and ATE within 90 days of COVID-19-associated hospitalization. A multivariable logistic regression model specifically for VTE was built using a priori determined clinical risk factors. A simplified RAM was derived and internally validated using bootstrap. RESULTS: From March 17, 2020 to November 30, 2020, 2804 hospitalized patients were analyzed. The incidence of VTE and ATE was 7.6% and 3.9%, respectively. The incidence of VTE, but not ATE, was higher in patients receiving recent anti-cancer therapy. A simplified RAM for VTE was derived and named CoVID-TE (Cancer subtype high to very-high risk by original Khorana score +1, VTE history +2, ICU admission +2, D-dimer elevation +1, recent systemic anti-cancer Therapy +1, and non-Hispanic Ethnicity +1). The RAM stratified patients into two cohorts (low-risk, 0-2 points, n = 1423 vs. high-risk, 3+ points, n = 1034) where VTE occurred in 4.1% low-risk and 11.3% high-risk patients (c statistic 0.67, 95% confidence interval 0.63-0.71). The RAM performed similarly well in subgroups of patients not on anticoagulant prior to admission and moderately ill patients not requiring direct ICU admission. CONCLUSIONS: Hospitalized patients with cancer and COVID-19 have elevated thrombotic risks. The CoVID-TE RAM for VTE prediction may help real-time data-driven decisions in this vulnerable population.

Personalized video consent in Blepharoplasty: A new paradigm in the preoperative consent giving process.

BACKGROUND: Informed consent is not simply the signing of a form by the patient but more significantly, a process of an in-depth communication between the doctor and the patient. AIM: The written informed consent process typically involves reading a lengthy document involving the medical terms which at times lead to misinterpretation. Therefore, the current research envisages assessing the effectiveness and acceptability of the video consent tool athwart the traditional written consent procedure. METHODS: A retrospective questionnaire study was carried out with 30 patients posted for Blepharoplasty surgery between ages of 18-50 years. They were divided into two groups randomly. All the participants were given written consent. Video consent was taken additionally for group 2 subjects. All the participants received pre-validated questionnaire. The evaluation scale used was a 5-point Likert scale. RESULTS: People with video consent group were more satisfied with the consent process. It was noted that all the patients who received video consent were happier and understood the consent process better than patients with written consent only. CONCLUSION: The inference drawn from our study depicts that video consent is not just easy to understand and clarifies the doubts associated with the surgery but also significantly reduces the anxiety of the patient preoperatively. Also, in other 'quality of life' improving cosmetic procedures including rhinoplasty, face lift surgeries, jaw surgeries, botox, fillers, lasers etc., video consenting tool can be used to a maximum benefit. It is strongly recommended to adopt the practice of taking video consent format in all forms of cosmetic procedures.

Evaluation of efficacy of QR678® and QR678® Neo hair growth factor formulation in the treatment of persistent chemotherapy-induced alopecia caused due to cytotoxic chemotherapy-A prospective pilot study.

BACKGROUND: Cancers are one of the main reasons of morbidity and mortality globally. Chemotherapy-induced alopecia (CIA) is one of the most alarming, terrifying, and traumatic adverse effects. A range of therapeutic measures has been suggested to alleviate CIA, but at present, there is no accepted pharmacological therapy that can assure prevention or management. AIM: The aim of the present study was to evaluate the efficacy of QR 678 Neo® therapy in the treatment of persistent chemotherapy-induced alopecia in women and men treated with cytotoxic chemotherapy for breast and lung cancers, respectively. METHODS: A total of 8 male patients with history of lung cancer and 12 female patients with history of breast cancer in the age range of 25-60 years, with WHO classification of grade I and II persistent alopecia who had undergone chemotherapy treatment, were selected for the study. At each visit, 1.5 mL solution of QR 678® was injected into the scalp skin of patients. A total of 8 sessions were performed at an interval of 3 weeks each. All the patients were evaluated with standard global photography, video microscopic assessment, and patient self-assessment questionnaire at baseline, 6 months, and 1 year. RESULTS: Marked improvement was seen in the global assessment score at 6 months (mean-8) which was maintained even after 1 year. Mean score increase in hair count at 6 months was 12.71 which further increased at 1 year. High satisfaction score was given by patients for slowing of hair loss (mean = 4.2) and also for overall hair growth. For appearance and growth of hair, the mean value was 3.4 and 3.8, respectively. CONCLUSION: The formulation of QR 678® and QR 678® Neo showed to be significantly safe and efficient for chemotherapy-induced alopecia in both men and women. Improvement in hair growth was maintained even at 1 year of follow-up. No patient had any severe adverse effects, and injections were also easily bearable by most of them.

Biomarker-enhanced VTE risk stratification in ambulatory patients with cancer.

INTRODUCTION: Risk assessment models are used to stratify cancer patients according to their underlying risk of VTE. The CATS score has been shown to enhance VTE risk stratification as compared to the modified Khorana score by incorporating d-dimer and soluble p-selectin measurements. Our aim was to evaluate the performance of the CATS score with respect to VTE risk stratification. MATERIALS AND METHODS: Analysis of a subset of the AVERT trial population for whom biomarker data was available. All patients included in the AVERT trial were at increased risk of VTE based on a modified Khorana score of ≥2. Patients were stratified according to the modified Khorana score and CATS score. Kaplan-Meier analysis was used to calculate the 6-month cumulative probabilities of VTE. RESULTS: A total of 466 patients were included in the analysis, 229 and 237 patients in the placebo and apixaban arms, respectively. The 6-month cumulative probability of VTE among patients with a modified Khorana score ≥ 3 was 13% [95% CI 7 to 23], whereas it was 20% [95% CI 11 to 35] for patients with a CATS score ≥ 4. The absolute risk reduction achieved with apixaban VTE prophylaxis among patients with modified Khorana ≥2, modified Khorana ≥3 and CATS ≥4 was -5.9% [-10.9 to -0.8], -5.8% [-16.0 to 4.5] and -10.1% [-22.9 to 2.6], respectively. Apixaban VTE prophylaxis among patients with increasing modified Khorana or CATS scores was not associated with an increased risk of bleeding events. CONCLUSIONS: The use of a CATS score of ≥4 to identify ambulatory cancer patients at very high risk of VTE could enhance the benefit/risk ratio achieved with apixaban VTE prophylaxis.

QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study.

Current treatment modalities are limited in their approach and success for hair loss. QR 678 & QR 678 Neo are new formulations, consisting of a combination of growth factors and peptides. This study demonstrates safety analysis of QR 678 & QR 678 Neo formulation, using in vitro cytotoxicity assay and in vivo animal efficacy. METHODS: Factors including vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-1, keratinocyte growth factor, and copper tripeptide 1 (QR 678) or their biomimetic peptides (QR678 Neo) were suspended in a sterile injectable vehicle. The 3-2,5-diphenyl tetrazolium bromide assay was used to explore the cytotoxic effects of each factor used in the compositions in human keratinocyte cell and human fibroblast cell assays. An in vivo analysis, wherein study animals were given intradermal QR 678 & QR 678 Neo injections, was conducted to assess whether the formulations produce hair growth. Also, hair follicle viability was checked by intradermal injection of the pharmaceutical compositions in secondary alopecia. RESULTS: In both formulations, a positive response was observed with respect to the number of mice exhibiting hair growth at the injection sites. The injections caused retention of hair in a 0.25-cm radius around the injection site. On cytotoxicity study, all the factors were found to be safe in human keratinocyte cell and human fibroblast cell assay. A positive response was demonstrated in animals on treatment with the chemotherapeutic agent. CONCLUSIONS: Intradermal injections of QR 678 & QR 678 Neo hair growth factor formulations are a safe and efficacious option for alopecia. Results seem encouraging enough to warrant a trial in humans with secondary alopecia, post cancer chemotherapy.