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Introduction: Many countries from South-East Asia reported an epidemic of sino-orbital mucormycosis (SOM), otherwise a rare disease, during the coronavirus disease 2019 pandemic. SOM, a potentially fatal disease, is typically treated with orbital exenteration and systemic antifungals after metabolic stabilization. There is no clear evidence of survival benefit of exenteration in the literature, and thus, there have been attempts at globe conserving treatments like orbital infusion after limited debridement and intraorbital injections with Amphotericin B (IOAB). Methods: We conducted a prospective comparative interventional study at a tertiary eye care hospital to evaluate treatment outcomes with the use of adjunctive IOAB in cases of SOM with mild to moderate orbital disease. Results: Thirty-six patients of SOM with mild to moderate orbital disease were recruited in the study. In the intervention group, 23/26 (885%) eyes had stable orbital disease at the end of treatment (4–6 weeks). No deterioration in visual acuity was noted as a result of treatment. In 8/26 (30.77%) patients, inflammation was noted as a side effect of IOAB requiring temporary discontinuation of injections. The mean follow-up for cases was 14.2 months (range 12–15 months). 1/23 (4.35%) patients had relapse of orbital disease at 3 months. Twenty-one patients are alive on last follow-up. Of the patients who refused treatment (controls), 2/9 (22.22%) patients relapsed. One of these patients with relapse underwent exenteration, while the other was managed with IOAB. At a follow-up of 14 months (range 12–15 months), eight patients are alive. On evaluating the ocular parameters in salvaged eyes, improvement in extraocular movements was noted in 75–80% cases. The degree of proptosis and resistance to retropulsion did not change significantly. Conclusion: In the current study, an improvement in the globe salvage rates was noted in cases of SOM with mild to moderate orbital disease treated with adjunctive IOAB as compared to controls at a mean follow-up of 14 months, although it did not achieve statistical significance. The study supports the inclusion of IOAB in routine management of mild to moderate orbital disease.

Abstract Background The intersubject variability which was related to the genetic makeup was the major cause of change in pharmacological and pharmacokinetic behavior of same dosage form in varied human being. 3D printing technology will help therapy evolve and eliminate the limitations of conventional technologies. Nebivolol's (NBL)-limited oral bioavailability is mainly due to its poor aqueous solubility. The research aims to combine advanced 3D printing technology and nanotechnology to design customized therapy and enhance the functionality of NBL using a statistical approach. Results and discussion The results of the phase solubility indicated that NBL was a poorly aqueous soluble drug. Its solubility was increased by employing nanoparticle drug delivery, which is a promising solubility enhancement technique. The 32 full factorial design was employed to develop and optimize bionanoparticles (BNPs) by solvent evaporation technique using poly (lactic-co-glycolic acid 50:50) (PLGA 50:50) and poloxamer-407 as a surfactant. The BNPs were characterized by % encapsulation efficiency (% EE), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC), transmission electron microscope (TEM), zeta potential, polydispersity index (PDI), particle size, in vitro drug release, etc. The BNPs loaded of NBL were further incorporated into the multichannel 3D-controlled release tablets made by PVA filaments employing fused deposition modeling (FDM) technology optimized by central composite design (CCD). Multichannel 3D-printed bionanoparticles-loaded tablet (M3DPBT) was optimized using CCD. All designed M3DPBTs were evaluated for post-fabrication parameters. The optimized M3DPBT could release more than 85% NBL within 10 h. Conclusions The newly fabricated M3DPBT was found stable. The amount of PLGA 50:50 and Polaxomer was significant for developing BNPs. % infill and layer height were observed as critical for the designing M3DPBT. The combined novel 3D printing and nanotechnology technology will open a new direction for patient compliance and better therapeutic effects. Graphical abstract Designing and developing of M3DPBT is substantially improve the patient compliance and therapeutic effectiveness of Nebivolol.

Introduction: Anaemia and cancer are two non communicable diseases with high global prevalence. The presence of anaemia in cancer patients is common, and its aetiology is multifactorial. Aim: To analyse the clinical profile, type and severity of anaemia in non haematological malignancies and to determine how the presence of metastasis affects it. Materials and Methods: A cross-sectional study was conducted in the Department of General Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India, between January 2022 and December 2023. Out of 1,294 patients diagnosed with malignancy, 190 subjects were analysed. The study included patients over 18 years of age diagnosed with non haematological malignancies who had anaemia according to the World Health Organisation (WHO) definition {females with Haemoglobin (Hb)

Abstract Rationale Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. Objective Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. Methods We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). Results Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen’s Kappa = 0.47 ± 0.07; P

Arvind Thakkar,1 Sushma Chenreddy,1 Astrid Thio,1 Wael Khamas,2 Jeffrey Wang,1 Sunil Prabhu1 1Department of Pharmaceutical Sciences, College of Pharmacy, 2College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA, USA Abstract: Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. Keywords: pancreatic cancer, toxicity, chitosan-solid lipid nanoparticle, aspirin, curcumin, sulforaphane

Angeli Thakkar, Kenneth GJ Ooi, Nagi Assaad, Minas Coroneo Department of Ophthalmology, Prince of Wales Hospital, Sydney, NSW, Australia Abstract: This case report documents a 58-year-old male who presented to the clinic with a 12-month history of a burrowing sensation in his eyelids that he attributed to a parasitic infestation. After being extensively investigated and reviewed by relevant specialties, no evidence of parasitic infestation was found. He was diagnosed with and treated for blepharitis. Psychiatric referral for presumed delusional infestation (DI) was recommended. Despite this, he remained insistent in his belief of infestation, and was inevitably lost to follow-up. DI, previously known as delusional parasitosis, is a rare delusional disorder where affected individuals have a fixed, false belief that they have a parasitic infestation. Diagnosis can be challenging. Practitioners need to evaluate between primary and secondary DI carefully, as management differs depending on the etiology. Despite this, patients diagnosed with primary DI tend to be resistant to psychiatric referral. This report aims to optimize management by giving the reader a guideline for appropriate investigations and advice on patient approach. It is important to recognize hallmark features of DI to minimize self-inflicted trauma and associated psychosocial consequences. Effective treatment for DI is available, and devastating consequences, including blindness, can be avoided. Keywords: delusions, parasitosis, infestation, ocular trauma

Pancreaticobiliary maljunction (PBM) is a congenital anomaly where the pancreatic and bile ducts join outside the duodenal wall, resulting in formation of an elongated common channel. In normal physiology, the sphincter of Oddi regulates the junction between the pancreatic and bile ducts. Individuals with PBM lack this regulatory mechanism resulting in reflux of pancreatic juices into the biliary tract. Activated pancreatic enzymes result in chronic inflammation of biliary tract resulting in choledochal cysts which places patients at risk for eventual development of cholangiocarcinoma.A 45-year-old white male presented with jaundice and dark urine. Laboratory tests showed elevated liver enzymes and bilirubin. Diagnostic imaging revealed anomalous biliary anatomy, a Type 1A choledochal cyst, and a mass in the common hepatic duct. Extrahepatic cholangiocarcinoma was confirmed by ERCP and biopsy, with PET/CT indicating localized disease without distant metastases.Treatment included a biliary sphincterotomy, stone drainage, and stenting. The patient underwent a robotic-assisted bile duct resection, cholecystectomy, hepatic lobectomy, and Roux-en-Y hepaticojejunostomy. The surgical specimen showed an invasive, poorly differentiated adenosquamous carcinoma with perineural invasion, but no regional lymph node involvement.PBM is a rare condition, and its diagnosis and management necessitate a multidisciplinary team, including pancreaticobiliary surgeons, endoscopists, and radiologists. Accurate diagnosis hinges on the team's expertise. Radiologists must be aware of PBM and have a thorough understanding of the associated anatomy and imaging characteristics that may indicate high-risk dysplasia or malignancy.

Background: Neoadjuvant chemotherapy (NACT) is routinely used in all cases of locally advanced breast cancer and some cases of early breast cancer. We previously reported a pathological complete response (pCR) rate of 8.3%. With the increasing use of taxanes and human epidermal growth factor receptor 2 (HER2)-directed NACT, we conducted this study to understand the current pCR rate and its determinants. Methods: A prospective database of breast cancer patients who underwent NACT followed by surgery between January and December 2017 was evaluated. Results: Of the 664 patients, 87.7% were cT3/T4, 91.6% were grade III, and 89.8% were node-positive at presentation (54.4% cN1, 35.4% cN2). The median age was 47 years; median pre-NACT clinical tumor size was 5.5 cm. Molecular subclassification was 30.3% hormone receptor positive (HR+) HER2-, 18.4% HR+HER2+, 14.9% HR-HER2+, and 31.6% triple negative (TN). Both anthracyclines and taxanes were given preoperatively in 31.2% patients whereas 58.5% of HER2 positive patients received HER2-targeted NACT. The overall pCR rate was 22.4% (149/664), 9.3% in HR+HER2-, 15.6% in HR+HER2+, 35.4% in HR-HER2+, and 33.4% in TN. On univariate analysis, duration of NACT (P < 0.001), cN stage at presentation (P = 0.022), HR status (P < 0.001), and lymphovascular invasion (P < 0.001) were associated with pCR. On logistic regression, HR negative status (Odds ratio [OR] 3.314, P < 0.001), longer duration of NACT (OR 2.332, P < 0.001), cN2 stage (OR 0.57, P = 0.012), and HER2 negativity (OR 1.583, P = 0.034) were significantly associated with pCR. Conclusion: Response to chemotherapy depends on molecular subtype and duration of NACT. A low rate of pCR in the HR+ subgroup of patients warrants reconsideration of neoadjuvant strategies. Keywords: Breast cancer India, neoadjuvant chemotherapy, pathological complete response rate, Author(s): Shalaka Joshi (corresponding author) [1]; Qurratulain Chougle [1]; Jarin Noronha [1]; Rohini Hawaldar [2]; Nita Nair [1]; Vaibhav Vanmali [2]; Vani Parmar [1]; Purvi Thakkar [1]; Garvit Chitkara [1]; [...]

ABSTRACTBackground Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has been a dynamically changing virus, requiring the development of adapted vaccines. This study estimated the potential public health impact alternative vaccination strategies for COVID-19 in Singapore.Research Design and Methods The outcomes of alternative vaccination strategies with a future adapted vaccine were estimated using a combined Markov decision tree model. The population was stratified by high- and standard-risk. Using age-specific inputs informed by local surveillance data and published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations.Results Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 278,614 cases 21,558 hospitalizations, 239 deaths, Singapore dollars (SGD) 277 million in direct medical costs, and SGD 684 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (3%), hospitalizations (29%), infections (145%), direct costs (90%), and indirect costs (192%) compared to the base case.Conclusions Broader vaccination strategies using an adapted booster vaccine could have substantial public health and economic impact in Singapore.