A Rare Case of Drug-Induced Sweet Syndrome After Pembrolizumab Therapy.

Sweet syndrome is an uncommon inflammatory disorder characterized by the abrupt appearance of painful, erythematous papules, plaques, or nodules on the skin. Fever and leukocytosis frequently accompany the cutaneous lesions. In addition, involvement of the eyes, musculoskeletal system, and internal organs may occur. Sweet syndrome has been associated with a broad range of disorders. There are three subtypes: classical Sweet syndrome, malignancy-associated Sweet syndrome, and drug-induced Sweet syndrome. Classical Sweet syndrome is not associated with malignancy or drugs. It is essentially associated with an upper respiratory infection, gastrointestinal infection, inflammatory bowel disease, and pregnancy. Malignancy-associated Sweet syndrome is associated with hematologic malignancy more than solid malignancy, most commonly with acute myeloid leukemia. Drug-induced Sweet syndrome usually develops approximately two weeks after drug exposure, in patients who lack a prior history of exposure to the inciting drug. Here we are discussing our patient, a 68-year-old male who presented eight weeks after starting chemotherapy with pemetrexed, carboplatin, and pembrolizumab for left lung adenocarcinoma with macular rash. On further investigation with biopsy was found to have neutrophilic dermatitis, hence being diagnosed with drug-induced Sweet syndrome. Histopathology revealed a dermis with infiltration of neutrophils with lekocytoclasia.

Derivatization-Based Novel Chromatographic and Spectrophotometric Methods for the Simultaneous Determination of Gymnemic Acid and Resveratrol in Antidiabetic Polyherbal Formulation.

Herbal medicine is widely used for the treatment and prevention of various ailments, highlighting the importance of ensuring its consistency and quality. This research focuses on the simultaneous detection of Gymnemic acid (GYM) and Resveratrol (RES) in an antidiabetic polyherbal formulation as no reported method exists for their simultaneously detection. The objective of this study is to develop and validate novel derivatization-based spectrometric and HPTLC methods for the simultaneous determination of GYM and RES. The spectrophotometric method involved derivatization of GYM with benzoyl chloride, followed by measurement of absorbance at 349 nm an isoabsorptive point. The HPTLC method utilized post derivatization with vanillin-sulfuric acid, and its separation was achieved on pre-coated silica gel 60GF254 using chloroform:methanol:glacial acetic acid (13:4:0.1, v/v/v) as mobile phase and estimated at 575 nm. The developed method exhibits linearity, accuracy, precision, LOD, LOQ, specificity and robustness in accordance with the ICH Q2 (R1) guideline. The percent assay of GYM and RES in the marketed capsule formulation was statistically compared using an unpaired t-test, resulting in a range of 99.51-102.65%. These indicate no significant difference between the proposed method and the marketed formulation. Therefore, both novel methods can be interchangeably used for quality control of GYM and RES in polyherbal formulations.

Uremic pruritus: prevalence, determinants, and its impact on health-related quality of life and sleep in Indian patients undergoing hemodialysis.

BACKGROUND: Uremic pruritus has an impact on the quality of life and sleep of hemodialysis patients, but the majority of cases go unreported and untreated unless severe, due to a lack of awareness. The purpose of this study is to determine the prevalence, associated factors, and impact on health-related quality of life (HR-QOL) and sleep in hemodialysis patients. METHODOLOGY: A single-center observational study of 3 months wherein 120 adults on maintenance hemodialysis were included. Baseline characteristics, dialysis-related factors, and lab parameters influencing uremic pruritus were recorded. Those with uremic pruritus completed "12-item pruritus severity scale (12-PSS)", "SKINDEX10", and "Itch-MOS" questionnaires to evaluate severity, impact on HR-QOL, and sleep respectively. RESULTS: Sixty seven over one hundred twenty (55.83%) patients had pruritus and majority were mild (40.83%) as per 12-PSS. Those with pruritus (n=67) had a mean age of 56.5±11.3 years, most were males (82%), chronic glomerulonephritis (29.1%) was the commonest cause of end-stage kidney disease, 3 active smokers, and 4 seropositive. 65(97%) patients were on twice-weekly dialysis, 36/67 had <5 years' dialysis vintage and acceptable adequacy. There was no significant association between uremic pruritus and dialysis-related/laboratory parameters. Patients with uremic pruritus demonstrated significantly worse "HR-QOL" (p<0.001) on the "SKINDEX-10", and patients' "Itch-MOS" scores demonstrated a significant decline in sleep quality with increasing pruritus severity (p<0.001). CONCLUSION: The majority of patients on maintenance hemodialysis experience uremic pruritus. None of the clinical characteristics, dialysis-related factors, and laboratory parameters affected uremic pruritus. Uremic pruritus patients had the worst HR-QOL & their sleep quality significantly declined as pruritus severity escalated. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Study approval was obtained from Institutional Research Committee and Institutional Ethical Committee (IEC 642/2021). Clinical Trial Registry of India (CTRI) registration (CTRI/2022/01/039143) was also obtained.

Identifying mutation hotspots reveals pathogenetic mechanisms of KCNQ2 epileptic encephalopathy.

Kv7 channels are enriched at the axonal plasma membrane where their voltage-dependent potassium currents suppress neuronal excitability. Mutations in Kv7.2 and Kv7.3 subunits cause epileptic encephalopathy (EE), yet the underlying pathogenetic mechanism is unclear. Here, we used novel statistical algorithms and structural modeling to identify EE mutation hotspots in key functional domains of Kv7.2 including voltage sensing S4, the pore loop and S6 in the pore domain, and intracellular calmodulin-binding helix B and helix B-C linker. Characterization of selected EE mutations from these hotspots revealed that L203P at S4 induces a large depolarizing shift in voltage dependence of Kv7.2 channels and L268F at the pore decreases their current densities. While L268F severely reduces expression of heteromeric channels in hippocampal neurons without affecting internalization, K552T and R553L mutations at distal helix B decrease calmodulin-binding and axonal enrichment. Importantly, L268F, K552T, and R553L mutations disrupt current potentiation by increasing phosphatidylinositol 4,5-bisphosphate (PIP2), and our molecular dynamics simulation suggests PIP2 interaction with these residues. Together, these findings demonstrate that each EE variant causes a unique combination of defects in Kv7 channel function and neuronal expression, and suggest a critical need for both prediction algorithms and experimental interrogations to understand pathophysiology of Kv7-associated EE.

Application of Lung Ultrasound in Critical Care Setting: A Review.

This article reviews the use of thoracic ultrasound in the intensive care unit (ICU). The focus of this article is to review the basic terminology and clinical applications of thoracic ultrasound. The diagnostic approach to a breathless patient, the blue protocol, is presented in a simplified flow chart. The diagnostic application of thoracic ultrasound in lung parenchymal and pleural diseases, role in bedside procedures, diaphragmatic assessment, and lung recruitment are described. Recent updates discussed in this review help support its increasingly indispensable role in the emergent and critical care setting.

Antibiotic Prescription Practices for Surgical Prophylaxis in India: An Observational Study.

Perioperative prophylactic antibiotics following surgeries have been shown to reduce surgical site infections, and their administration is common practice. Despite clear guidelines regarding this being set forth by the Infectious Disease Society of America (IDSA), adherence to them is yet to translate to common practice in many parts of the world. A retrospective chart review of 409 patients who underwent elective surgeries over a period of 7 months at three different hospitals in India was performed. In-hospital antibiotic prescriptions of these patients were examined for any apparent inappropriateness (use of antibiotics with coverage broader than the target microbes and use of antibiotics with overlapping spectrum of target microbes). Four hundred ninety-five (48.9%) of the 1,012 patient intensive care unit (ICU) days had apparent inappropriateness in the choice of their prophylactic antibiotics and only 3.2% of the antibiotic units used were in accordance with the present IDSA guidelines. Injudicious use of broad-spectrum antibiotics for surgical prophylaxis is prevalent in low- and middle-income countries such as India. This poses the risk of emergence of resistant microorganisms in these areas and their potential spread across the borders. There is an acute need for diligent antibiotic stewardship programs in these areas to curb such practices.

Use of home telemedicine for critical illness rehabilitation: an Indian success story.

One-fifth of healthcare beneficiaries in developed nations get discharged from hospitals to physician supervised skilled nursing care facilities. In low-income and middle-income countries like India, postdischarge skilled nursing facilities are at a very nascent stage and largely underequipped in terms of infrastructure, skilled nursing and physician staff to manage complicated patients. Hence the responsibility of management of such patients lies largely with their families. We present a case where a 26-year-old man with Duchenne Muscular Dystrophy who became ventilator dependent following major surgeries was weaned off his ventilator and rehabilitated back to his prehospital state. This was done at his home with visiting nurses and rehabilitation services under telemedicine supervision by a critical care specialist. Use of telemedicine services could be a viable and cost-effective option to ensure adherence to evidence-based medicine and standardisation of care in resource limited countries such as India.

Customized 3D printing: A novel approach to migrated orbital implant.

This paper describes a novel approach to treat migrated orbital implants post socket surgery. Implant migration may hinder the final aesthetic outcome of a custom ocular prosthesis. Once an implant migrates within the orbit there tends to be fibrosis around the implant. This fibrosis does not allow for centeration of the implant during repeat surgery. Hence treatment of a migrated implant traditionally involves implant removal with dermis fat grafting. Dermis fat graft though an option, needs a second site surgery that may be unacceptable to many patients. Also the rate of graft necrosis is as high as 40%. This paper describes a technique to create a custom orbital implant that allows recenteration of the migrated implant centrally, using 3-dimension (3D) printing and rapid prototyping to construct the patients affected orbit. This orbit is used as a mould to create the custom orbital implant that aids in volume augmentation as well as recenteration of the migrated orbital implant.

Predicting 30-Day All-Cause Readmission Risk for Subjects Admitted With Pneumonia at the Point of Care.

BACKGROUND: The pneumonia 30-d readmission rate has been endorsed by the National Quality Forum as a quality metric. Hospital readmissions can potentially be lowered by improving in-hospital care, transitions of care, and post-discharge disease management programs. The purpose of this study was to create an accurate prediction model for determining the risk of 30-d readmission at the point of discharge. METHODS: The model was created using a data set of 1,295 hospitalizations at the Cleveland Clinic Main Campus with pneumonia over 3 y. Candidate variables were limited to structured variables available in the electronic health record. The final model was compared with the Centers for Medicare and Medicaid Services (CMS) model among subjects 65 y of age and older (n = 628) and was externally validated. RESULTS: Three hundred thirty subjects (25%) were readmitted within 30 d. The final model contained 13 variables and had a bias-corrected C statistic of 0.74 (95% CI 0.71-0.77). Number of admissions in the prior 6 months, opioid prescription, serum albumin during the first 24 h, international normalized ratio and blood urea nitrogen during the last 24 h were the predictor variables with the greatest weight in the model. In terms of discriminative performance, the Cleveland Clinic model outperformed the CMS model on the validation cohort (C statistic 0.69 vs 0.60, P = .042). CONCLUSIONS: The proposed risk prediction model performed better than the CMS model. Accurate readmission risk prediction at the point of discharge is feasible and can potentially be used to focus post-acute care interventions in a high-risk group of patients.

Lung Transplantation After 125 Days on ECMO for Severe Refractory Hypoxemia With No Prior Lung Disease.

Venovenous extracorporeal membrane oxygenation (ECMO) has become a viable and increasingly utilized option for the treatment of refractory hypoxemia in severe acute respiratory distress syndrome (ARDS). However, options are limited for ARDS patients who fail to wean from ECMO. The high rates of infection, presence of extrapulmonary end organ damage, intensive care unit-acquired weakness, and high short-term mortality associated with ARDS are all significant hurdles that make lung transplantation a difficult prospect to consider. However, ECMO support has been used as a bridge to transplant in patients with other underlying chronic lung diseases. Our case illustrates the successful use of lung transplantation for a patient with no previous lung disease who developed refractory ARDS requiring protracted ECMO support. The use of ambulatory ECMO with early institution of physical therapy is an essential component in preparing such patients for successful transplantation.

Pediatric Perimeter-A Novel Device to Measure Visual Fields in Infants and Patients with Special Needs.

PURPOSE: There are no commercially available devices to measure visual fields in infants. We developed a device, "Pediatric Perimeter," that quantifies visual field extent (VFE) for infants. We describe the construction, validation, and use of this device. METHODS: A hemispherical dome with light emitting diodes (LEDs) was constructed. The LEDs were controlled using a computer program to measure reaction time (RT) to gross visual fields (GVF) and the VFE. Participants were tested in supine position in a dark room. Eye or head movement towards the stimuli was monitored with an infrared (IR) camera. Validation was done on 10 adults (mean age: 24.4 ± 5 years) with tunnel vision simulator. RESULTS: Perimetry was performed on 19 infants (age: 2.3-12 months), five infants with normal milestones. GVF and VFE were estimated in 17 and 7 infants, respectively. Median RT of infants with developmental delay was 663 ms and 380 ms for healthy infants. Also, 14 children (age: 14 months-6 years) with developmental delay and five patients with cognitive impairment were tested. CONCLUSION: Visual field isopter and RT can be examined with the Pediatric Perimeter device on infants and patients with special needs. Further testing on infants will need to assess the repeatability. A large-scale study will be needed to compare typically developing infants and infants with delayed milestones with this device. TRANSLATIONAL RELEVANCE: Quantifiable parameters obtained with this device can be used as outcome measures in clinical examination of infants and patients with special needs. This device can be used in pediatric, neurology, and ophthalmology clinics.

Critical illness associated with 2013-2014 influenza A (H1N1): Postpandemic characteristics, presentation and outcomes.

INTRODUCTION: The United States experienced a postpandemic outbreak of H1N1 influenza in 2013-2014. Unlike the pandemic in 2009 clinical course and outcomes associated with critical illness in this postpandemic outbreak has been only sparsely described. METHODS: We conducted a retrospective analysis of all patients admitted to the Medical Intensive Care Unit with H1N1 influenza infection in 2009-2010 (pandemic) and 2013-2014 (postpandemic). RESULTS: Patients admitted in the postpandemic period were older (55 ± 13 vs. 45 ± 12, P = 0.002), and had a higher incidence of underlying pulmonary (17 vs. 7, P = 0.0007) and cardiac (16 vs. 8, P = 0.005) disease. Mechanical ventilation was initiated in most patients in both groups (27 vs. 21, P = 1.00). The PaO2/FiO2 ratio was significantly higher in the pandemic group on days 1 (216 vs. 81, P = 0.0009), 3 (202 ± 99 vs. 100 ± 46, P = 0.002) and 7 (199 ± 103 vs. 113 ± 44, P = 0.019) but by day 14 no difference was seen between the groups. Rescue therapies were used in more patients in the postpandemic period (48% vs. 20%, P = 0.028), including more frequent use of prone ventilation (10 vs. 3, P = 0.015), inhaled vasodilator therapy (11 vs. 4, P = 0.015) and extracorporeal membrane oxygenation (ECMO) (4 vs. 2, P = NS). No significant differences in mortality were seen between the two cohorts. CONCLUSIONS: Compared to the 2009-2010 pandemic, the 2013-2014 H1N1 strain affected older patients with more underlying co-morbid cardio-pulmonary diseases. The patients had worse oxygenation indices and rescue modalities such as prone ventilation, inhaled epoprostenol and ECMO, were used more consistently as compared to the 2009 pandemic.