Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024.

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent's toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.

Comparison of risk factors for Methicillin Resistant Staphylococcus aureus (MRSA) colonization in healthy newborns, born to mothers with and without MRSA colonization.

Objective: To compare the risk factors for MRSA colonization in healthy newborns, born of mothers with and without MRSA colonization. Methods: This case control study was conducted in post-natal unit of Lady Willingdon Hospital, affiliated with King Edward Medical University/Mayo Hospital, Lahore from January to June 2017. The vaginal and anterior nares swabs for MRSA culture were collected from mothers within six hours before planned delivery and the neonatal anterior nares swabs for MRSA culture were taken within one hour of birth. All the samples were cultured in Paediatric Microbiology laboratory in Mayo Hospital. Data were analyzed through SPSS 20.0 and logistic regression was applied for risk factors analysis. Results: Out of total 80 mothers and their newborns, 15 (18.75%) mothers and 16 neonates (20%) were MRSA colonized. The frequency of MRSA colonization in mothers' anterior nares and vaginal swab was 17.5% and 1.25% respectively. The significant risk factors were prolonged rupture of membranes for >18 hours (p-value 0.02, odds ratio 11.85, 95% CI 1.41-99.3), birth weight <2500 grams (p-value 0.01, odds ratio 5.39, 95% CI 1.35-21.4), history of presence of meconium (p-value 0.006, odds ratio 7.30, 95% CI 1.78-29.8). The non-significant factors were age of mother (p-value 0.682, odds ratio 0.765, 95% CI 1.0.212-2.76), parity (p-value 0.185, odds ratio 3.82, 95% CI 0.46-31.66) , gestation (p-value 0.615, odds ratio 0.797, 95% CI 0.714-0.89) , mode of delivery (p-value 0.576, odds ratio 0.543, 95% CI 0.062-4.76), sex of baby (p-value 0.546, odds ratio 0.683, 95% CI 0.196-2.37) and presentation of baby at birth (p-value 0.47, odds ratio 0.795, 95% CI 0.71-0.89). Conclusion: The presence of meconium, prolonged rupture of membranes and low birth weight were the significant risk factors for MRSA colonization in healthy new-borns, born to mothers with and without MRSA colonization.

Age and sex-related comparison of referral-based telemedicine service utilization during the COVID-19 pandemic in Ontario: a retrospective analysis.

BACKGROUND: The COVID-19 pandemic has led to increased utilization of telemedicine services. METHODS: A retrospective analysis of all referral-based ambulatory telemedicine services in Ontario from November 2019 to June 2021 was collected from the Ontario Health Insurance Plan (OHIP) billing database. Only fee-for-service billings were included in the present analysis. Coincident COVID-19 cases were obtained from Public Health Ontario. Comparisons were made based on age bracket, sex, telemedicine and in-person care. RESULTS: Billings for telemedicine services in Ontario increased from $1.7 million CAD in November 2019 to $64 million CAD in April 2020 and the proportions reached a mean peak of 72% in April 2020 and declined to 46% in June 2021. A positive correlation was found between the use of telemedicine and COVID-19 cases (p = 0.05). The age group with the highest proportion of telemedicine use was the 10-20-year-olds, followed by the 20-50-year-olds (61 ± 9.0%, 55 ± 7.3%, p = 0.01). Both age groups remained above 50% telemedicine services at the end of the study period. There seemed to be higher utilization by females (females 54.2 ± 8.0%, males 47.9 ± 7.7%, ANCOVA p = 0.05) for all specialties, however, after adjusting for male to female ratio m:f of 0.952:1.0 according to the 2016 census, this was no longer significant. CONCLUSIONS: The use of telemedicine services remained at a high level across groups, particularly the 10-50-year-olds. There were clear age preferences for using telemedicine. Studying these differences may provide insights into how the delivery of non-hospital-based medicine has changed during the COVID-19 pandemic.

Stakeholders' views and opinions on existing guidelines on "How to Choose Mental Health Apps".

Background: Mental health Applications (Mhealth Apps) can change how healthcare is delivered. However, very little is known about the efficacy of Mhealth Apps. Currently, only minimum guidance is available in Assessment and Evaluation Tools (AETs). Therefore, this project aims to understand AET developers' perspectives and end users' experiences and opinions on "how to choose a Mhealth App". Objective: The primary objectives were: (1) obtaining stakeholder's opinions and experiences of development and use of AETs for Mhealth Apps, their weaknesses and strengths, and barriers in their implementation of Mhealth Apps; (2) the experiences of App users, their analyzation and, obstacles in the use of apps; and (3) to quantify themes related to choosing a Mhealth App. Methods: This qualitative study, used a sampling method to recruit six stakeholders (one App developer, two AET developers, an individual with lived experience of mental health illness, and two physicians) who were interviewed using a topic guide. These were examined by researchers (CT, WK, & FN) using thematic content analysis. Additionally, an anonymous online survey of 107 individuals was conducted. Findings: Our analyses revealed six main themes: (a) needs and opportunities; (b) views on Mhealth apps; (c) views & opinions on AETs; (d) implementation barriers; (e) system of evaluation and; (f) future directions. The first key concept was, all stakeholders agreed that Apps could significantly impact mental health and that end-users were unaware of mental health AETs and Apps. Secondly, due to commercial interests, end-users reliability of App evaluations requires clear conflict-free guidelines. Thirdly, AETs should be evaluated and developed through a rigorous methodology. Finally, stakeholders shared insights into future developments for AETs and Mhealth Apps. Additionally, online survey respondents chose a "health professional" as their preferred source of guidance in selecting a Mhealth app (84%) and best suited to develop guidelines (70%). Conclusion: The interviews and survey highlight the need for Mhealth Apps to be regulated and the importance of health professionals' engagement in the implementation process. Similarly, without well-defined roles for App evaluations within the health care system, it is unlikely that AETs will have wider spread use and impact without risk.

Study Comparing Topical Ivermectin Versus Topical Permethrin in the Treatment of Scabies.

Introduction Scabies is a highly contagious skin disease caused by an ectoparasite mite called Sarcoptes scabiei. Ivermectin and permethrin have been commonly used for the treatment of scabies. However, topical ivermectin has been compared to other treatment modalities to a lesser extent. Objective This study aimed to compare the efficacy of topical ivermectin versus topical permethrin in the treatment of uncomplicated scabies. Methods 354 patients with scabies attending the dermatology outpatient department of Pak Emirates Military Hospital Rawalpindi were enrolled. Patients were divided into two groups randomly. The first group and their family contacts received 1% ivermectin lotion whereas the other received 5% permethrin lotion. Patients were evaluated at the end of the second and the fourth week. Results At the end of the second week, initial follow-up showed that 97 out of 159 patients (61.0%) in the ivermectin 1% group, and 107 out of 159 patients (67.3%) in the permethrin 5% group had achieved clinical cure (P=0.24). On the final follow-up at the end of Week 4, the cure rate amounted to 85.5% (136 of 159 patients) in the ivermectin group and 89.9% (143 of 159 patients) in the permethrin group. Differences among both groups remained statistically insignificant (P=0.23). Conclusions The use of ivermectin 1% versus permethrin 5% as topical therapy showed almost identical results for the treatment of uncomplicated scabies. Side effects were minimal and there were no significant differences observed in patients with regard to compliance among both the groups.

Post-graduate educational environment of two parallel programs in Pediatric Medicine.

Objective: To compare the trainees' perception of the Educational Environment (EE) of the two parallel post-graduate training programs (MD & FCPS) in Pediatric Medicine. Methods: This quantitative cross-sectional study was carried out by Department of Medical Education UOL and Department of Pediatric Medicine KEMU from February to December 2021. Data about the perception of EE was collected from the Pediatric Medicine trainees by purposive sampling using the 40 items PHEEM inventory. The inventory has three perception domains: role autonomy, teaching, and social support. In addition, to mean scores, the inventory also gives interpretation according to the score ranges. The FCPS and MD trainees of both genders and all years of training across the institutions of Punjab were approached using Google Forms. SPSS (v 23.0) was used for descriptive and analytic statistics. Results: A total of 327 trainees' responses were included-188 (57.5%) FCPS and 139 (42.5%) MD trainees. The mean overall score was 92±19.7 for FCSP and 93.88±21.5 for MD trainees (p-value 0.41). The interpretation of the overall score was "more positive than negative but room for improvement" in 67.3%. For the subscales of role autonomy, teaching, and social support, the perception was positive by 71%, 80%, and 45% of trainees, respectively. Except for three individual items, the mean scores of the subscales and the individual items were not statistically different between the two groups. Conclusion: The Pediatric Medicine trainees' perception of the educational environment in the FCPS and MD groups was comparable overall and in all three domains. Individual item analysis showed almost similar areas for improvement in both programs.

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 6.2023.

Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

Rise in the Number of Complex Skin Cancers Necessitates Establishing Mohs Micrographic Surgery Fellowships in Pakistan.

As more and more patients seek treatment for increasingly complicated and cosmetically challenging skin cancers, Mohs Micrographic Surgery (MMS) is now exceedingly in demand. Training in MMS could help dermatologists improve patient outcomes allowing them to handle complex lesions safely and efficiently and hence, provide the best possible care. As a result, there is an urgent need to train additional dermatologists in Mohs Surgery in order to meet the huge demand for dermatologists with imperative expertise, specifically in this field.

Frequency, geographical distribution and outcomes of pit viper bites in Malaysia consulted to Remote Envenomation Consultancy Services (RECS) from 2017 to 2020.

Not all pit viper species are present in every state of Malaysia and their distribution varies according to altitude. There is limited information on pit viper bite incidence and its geographical distribution. This was a cross-sectional study of confirmed pit viper bite cases referred to Remote Envenomation Consultancy Services (RECS) from January 2017 to December 2020. Data was collected following the approval of institutional research ethics committee. Universal sampling methods were used. Confirmed pit viper bite cases in each state, geographical location and the antivenom used were reported. A total of 523 confirmed pit viper bite injuries occurred over the 4-year study period. The majority were Malaysians, male and young adults. Most were non-occupational related (83.9%) and involved the upper limbs (46.8%). The commonest pit viper species involved was Trimeresurus purpureomaculatus (23.7%). Green pit viper antivenom (GPAV) was the most frequent antivenom used (n = 51) with the majority of patients requiring only one dose (3 vials). This study provides a better appreciation of indigenous pit viper species distribution for each state and reflects the requirement of appropriate antivenom to be stocked in each state or district hospital.

DR-NASNet: Automated System to Detect and Classify Diabetic Retinopathy Severity Using Improved Pretrained NASNet Model.

Diabetes is a widely spread disease that significantly affects people's lives. The leading cause is uncontrolled levels of blood glucose, which develop eye defects over time, including Diabetic Retinopathy (DR), which results in severe visual loss. The primary factor causing blindness is considered to be DR in diabetic patients. DR treatment tries to control the disease's severity, as it is irreversible. The primary goal of this effort is to create a reliable method for automatically detecting the severity of DR. This paper proposes a new automated system (DR-NASNet) to detect and classify DR severity using an improved pretrained NASNet Model. To develop the DR-NASNet system, we first utilized a preprocessing technique that takes advantage of Ben Graham and CLAHE to lessen noise, emphasize lesions, and ultimately improve DR classification performance. Taking into account the imbalance between classes in the dataset, data augmentation procedures were conducted to control overfitting. Next, we have integrated dense blocks into the NASNet architecture to improve the effectiveness of classification results for five severity levels of DR. In practice, the DR-NASNet model achieves state-of-the-art results with a smaller model size and lower complexity. To test the performance of the DR-NASNet system, a combination of various datasets is used in this paper. To learn effective features from DR images, we used a pretrained model on the dataset. The last step is to put the image into one of five categories: No DR, Mild, Moderate, Proliferate, or Severe. To carry this out, the classifier layer of a linear SVM with a linear activation function must be added. The DR-NASNet system was tested using six different experiments. The system achieves 96.05% accuracy with the challenging DR dataset. The results and comparisons demonstrate that the DR-NASNet system improves a model's performance and learning ability. As a result, the DR-NASNet system provides assistance to ophthalmologists by describing an effective system for classifying early-stage levels of DR.

An Automated Deep Learning Approach for Spine Segmentation and Vertebrae Recognition Using Computed Tomography Images.

Spine image analysis is based on the accurate segmentation and vertebrae recognition of the spine. Several deep learning models have been proposed for spine segmentation and vertebrae recognition, but they are very computationally demanding. In this research, a novel deep learning model is introduced for spine segmentation and vertebrae recognition using CT images. The proposed model works in two steps: (1) A cascaded hierarchical atrous spatial pyramid pooling residual attention U-Net (CHASPPRAU-Net), which is a modified version of U-Net, is used for the segmentation of the spine. Cascaded spatial pyramid pooling layers, along with residual blocks, are used for feature extraction, while the attention module is used for focusing on regions of interest. (2) A 3D mobile residual U-Net (MRU-Net) is used for vertebrae recognition. MobileNetv2 includes residual and attention modules to accurately extract features from the axial, sagittal, and coronal views of 3D spine images. The features from these three views are concatenated to form a 3D feature map. After that, a 3D deep learning model is used for vertebrae recognition. The VerSe 20 and VerSe 19 datasets were used to validate the proposed model. The model achieved more accurate results in spine segmentation and vertebrae recognition than the state-of-the-art methods.

Accurate Prediction of Anxiety Levels in Asian Countries Using a Fuzzy Expert System.

Anxiety is a common mental health issue that affects a significant portion of the global population and can lead to severe physical and psychological consequences. The proposed system aims to provide an objective and reliable method for the early detection of anxiety levels by using patients' physical symptoms as input variables. This paper introduces an expert system utilizing a fuzzy inference system (FIS) to predict anxiety levels. The system is designed to address anxiety's complex and uncertain nature by utilizing a comprehensive set of input variables and fuzzy logic techniques. It is based on a set of rules that represent medical knowledge of anxiety disorders, making it a valuable tool for clinicians in diagnosing and treating these disorders. The system was tested on real datasets, demonstrating high accuracy in the prediction of anxiety levels. The FIS-based expert system offers a powerful approach to cope with imprecision and uncertainty and can potentially assist in addressing the lack of effective remedies for anxiety disorders. The research primarily focused on Asian countries, such as Pakistan, and the system achieved an accuracy of 87%, which is noteworthy.

Evaluation of the Resources and Inequities Among Pediatric Critical Care Facilities in Pakistan.

OBJECTIVES: To evaluate nationwide pediatric critical care facilities and resources in Pakistan. DESIGN: Cross-sectional observational study. SETTING: Accredited pediatric training facilities in Pakistan. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A survey was conducted using the Partners in Health 4S (space, staff, stuff, systems) framework, via email or telephone correspondence. We used a scoring system in which each item in our checklist was given a score of 1, if available. Total scores were added up for each component. Additionally, we stratified and analyzed the data between the public and private healthcare sectors. Out of 114 hospitals (accredited for pediatric training), 76 (67%) responded. Fifty-three (70%) of these hospitals had a PICU, with a total of 667 specialized beds and 217 mechanical ventilators. There were 38 (72%) public hospitals and 15 (28%) private hospitals. There were 20 trained intensivists in 16 of 53 PICUs (30%), while 25 of 53 PICUs (47%) had a nurse-patient ratio less than 1:3. Overall, private hospitals were better resourced in many domains of our four Partners in Health framework. The Stuff component scored more than the other three components using analysis of variance testing ( p = 0.003). On cluster analysis, private hospitals ranked higher in Space and Stuff, along with the overall scoring. CONCLUSIONS: There is a general lack of resources, seen disproportionately in the public sector. The scarcity of qualified intensivists and nursing staff poses a challenge to Pakistan's PICU infrastructure.

A prospective study on linking diarrheagenic E. coli with stunted childhood growth in relation to gut microbiome.

Stunted growth is an emerging global challenge affecting children under the age of 5 years in low- and middle-income countries. Despite such a high global prevalence of stunting, the mechanism of pathogenesis and the role of associated gut microbiota is poorly understood. The present study was designed to investigate the association of pathogenic strains of E. coli with the residential gut microbiota of stunted growth children. A total of 64 stool sample were collected from children aged ≤ 5 years, and were processed for isolation and molecular characterization of diarrheagenic E. coli. Selected stool samples (n = 39 including three normal controls) were then analysed for microbial community profiling using 16S ribosomal RNA (rRNA) gene sequencing. Furthermore, associations between changes in the microbiota in the presence of different E. coli strains was explored. Pathotyping of the isolated E. coli (n = 64) has shown that 39.68% belonged to one of the five pathotypes of E. coli whilst the remaining ones were non-typeable. Amongst the different pathotypes, EPEC was found to be the most prevalent (52%; n = 13), followed by EAEC (20%; n = 5), EIEC (12%; n = 3), EHEC (8%; n = 2) and ETEC 2 (8%; n = 2). Phylogrouping analysis has shown that majority of the strains belonged to B2 (28.12%). Microbial diversity is shown to be significant and varied when the samples are organized under the recovered phylogroups. Moreover, based on predictive metabolism, the colonization of these strains were found to be significantly associated with energy utilization pathways such as Denovoprine-2 and glyoxylate-by. Differential analysis has shown that Escherichia-Shigella and Enterococcus were altered for the children with stunted growth.

Endogenous Endopthalmitis in Disseminated Methicillin-Sensitive Staphylococcus aureus (MSSA) Bacteremia.

Endogenous endophthalmitis (EE) is an ocular infection resulting from hematogenous spread from the remote primary source. Risk factors include endocarditis, bacteria meningitis, immunosuppressive state, and invasive procedures in patients with sepsis. We present a case of a 43-year-old gentleman with poorly controlled diabetes mellitus who was admitted for bilateral nasoseptal cellulitis with a right nasal wall abscess and right vocal cord palsy. At presentation, he just had preseptal cellulitis without any posterior segment involvement. He underwent incision and drainage under the Otorhinolaryngology team. Unfortunately, postoperatively he developed sepsis with a hematogenous spread of infection systemically involving his right eye (endophthalmitis) and his heart valve (infective endocarditis). Blood culture revealed Methicillin Sensitive Staphylococcus Aureus (MSSA) infection. He had six weeks of intravenous cloxacillin and three times intravitreal injections of vancomycin and ceftazidime with complete resolution of signs and symptoms. In the case of a poorly controlled diabetic patient with an extensive regional infection, the presence of ocular symptoms and signs that are suggestive of EE must be taken seriously and warrant a complete eye examination as early detection and treatment of EE is crucial for better prognosis.

Coronoid fixation and lateral collateral ligament repair in varus posteromedial rotatory instability of the elbow.

Background: Varus posteromedial rotatory instability is a relatively rare elbow injury, that has been infrequently reported in published literature. We intended to evaluate the outcomes of surgical management of this rare injury with anteromedial coronoid fixation, and, in selected patients, lateral ulnar collateral ligament (LUCL) repair. Methods: Between 2017 and 2020, we identified 12 patients with anteromedial coronoid fractures, and a varus posteromedial rotatory instability, who underwent surgery for fixation of the coronoid fracture, with or without LCL repair. All the included patients were either O'Driscoll subtype 2-2, or subtype 2-3. All the 12 patients were followed up for a minimum of 24 months, and their functional outcomes assessed using the Mayo Elbow Performance Score (MEPS). Results: The mean MEPS recorded in our study was 92.08, and the mean range of elbow flexion achieved was 124.2°. The mean flexion contracture in our patients was 5.83°. Three of our twelve patients (25%) suffered from elbow stiffness even at final follow-up. The results were graded as Excellent in eight, Good in three, and Fair in one patient. Conclusion: Coronoid fractures and LUCL disruptions associated with varus posteromedial rotatory instability can be reliably managed by employing a protocol that combines radiographic parameters, as well as intra-operative assessments of stability. While surgical intervention successfully restored stability, there is a learning curve to the management of these injuries and complications are not uncommon, particularly elbow stiffness. Hence, in addition to surgical fixation, emphasis should also be placed on intensive post-operative rehabilitation to improve outcomes.

COVID-19 Vaccination in Pregnant Women: Exploring Serious Adverse Events.

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Frequency, clinical characteristics and outcomes of Tropidolaemus species bite envenomations in Malaysia.

Pit vipers from the genus Tropidolaemus are identified as one of the common causes of snake bite from venomous species in Malaysia. All Tropidolaemus species bite cases referred to the Remote Envenomation Consultation Services (RECS) between 2015-2021 were included. A total of 4,718 snake-related injuries cases consulted to RECS with 310 (6.6%) involved Tropidolaemus species; of these 190 (61.3%) were T. subannulatus and 120 (38.7%) T. wagleri. All the T. subannulatus cases occurred in Sabah and Sarawak while all cases of T. wagleri occurred in Peninsular Malaysia. The majority of patients were male (74.8%) and adults between 18-59 years old (61.2%). The upper limb (56.6%) was the most frequent anatomical region involved. Most cases were non-occupationally related (75.4%). Bites from both species caused local pain (77.1%) and swelling (27.2%). Most patients complained of mild pain (48.0%). Paracetamol (40.0%) was the most common analgesic prescribed. Antivenom was not indicated in all cases. Two patients were given antivenom inappropriately before RECS consultation. Most patients (54.7%) needed hospital observation for less than 24 hours. No deaths occurred in the group studied.

Unusual presentation of gastric cancer during treatment of hairy cell leukemia: Exploring the etiological basis of this rare phenomenon.

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder. Patients typically present with cytopenia and splenomegaly. We describe the case of a 78-year-old patient with refractory HCL who acutely developed a cystic lesion on the back while receiving moxetumomab pasudotox therapy. Biopsy of the lesion revealed the presence of adenocarcinoma, which prompted a detailed evaluation resulting in a diagnosis of stage IV gastric cancer. Nevertheless, to establish any association between moxetumomab pasudotox therapy and secondary cancer development, a satisfactory number of studies need to be conducted.

Pembrolizumab-Induced Lichen Planus in a Patient With Non-Small-Cell Lung Carcinoma (NSCLC) That Correlates to Therapeutic Response.

Immune checkpoint inhibitors are increasingly being used in the treatment of various solid organ and hematologic malignancies. Dermatologic toxicities associated with programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) therapy have been widely reported in the literature. Lichen planus is an inflammatory disease frequently seen in areas of the skin and oral mucous membrane lining. This autoimmune disorder is T-cell mediated with multiple contributing factors like emotional stress, genetic predisposition, isotopic response, or drugs. With increasing use of immunotherapy, early recognition and prompt treatment of associated adverse events are critical to ensure patient safety. Cutaneous toxicities are among the most commonly observed adverse events with this class of drugs. Here, we report a case of lichen planus in a 66-year-old male patient receiving pembrolizumab for stage IV non-small cell lung cancer (NSCLC). He was diagnosed 56 months ago with advanced lung cancer with brain metastasis. He has received 62 cycles of pembrolizumab and continues to be in complete clinical and radiographic remission. Pembrolizumab is a drug that helps immune cells in killing cancer cells by binding to the PD-1 protein. This case highlights the potential cutaneous side effects that may result in a patient with pembrolizumab and the fact that it can serve as a "clinical biomarker" and show therapeutic effectiveness of the treatment.