Supplemental Intravitreal Ranibizumab Injections in Eyes Treated with the Port Delivery System with Ranibizumab in the Archway Trial.

PURPOSE: To determine the proportion and characteristics of eyes with neovascular age-related macular degeneration (nAMD) treated with the Port Delivery System with ranibizumab (PDS) that receive supplemental intravitreal ranibizumab injections due to changes in best-corrected visual acuity (BCVA) and/or central subfield thickness (CST), and to investigate the safety and efficacy of supplemental injections in eyes with the PDS. DESIGN: Post-hoc analyses of data from the phase 3, randomized, multicenter, open-label, active-comparator Archway trial (NCT03677934). PARTICIPANTS: Adults with nAMD diagnosed within 9 months of screening previously responsive to anti-vascular endothelial growth factor (anti-VEGF) therapy. INTERVENTION: 418 patients were randomized to the PDS with ranibizumab 100 mg/mL with fixed refill-exchanges every 24 weeks (Q24W) or monthly intravitreal ranibizumab 0.5 mg for 96 weeks. RESULTS: Of the 246 eyes treated with the PDS Q24W and assessed for supplemental treatment criteria, the vast majority (94.6%-98.4%) did not receive supplemental treatment during each retreatment interval, with 87.4% not receiving supplemental treatment at any point during the trial. Of the 31 eyes receiving supplemental treatment, 58.1% received 1 injection and 32.3% received 2. At baseline, eyes receiving supplemental treatment were significantly more likely to have thicker retinas (mean CST 370.5µm vs 304.4µm; P = 0.0001), subretinal fluid (54.8% vs 21.2%; P < 0.0001), and larger pigment epithelial detachment height (215.7µm versus 175.9µm; P = 0.003). These features have previously been associated with difficult-to-treat nAMD. Whereas BCVA and CST generally remained constant throughout the trial in eyes without supplemental treatment, the small number of eyes receiving supplemental treatment on average lost 1 line of vision from baseline to week 96 (mean -5.7 Early Treatment Diabetic Retinopathy Study score letters) and CST continued to increase over time. Absolute BCVA at week 96 was similar irrespective of supplemental treatment status (71.1 and 73.7 letters). BCVA and CST generally improved within 28 days of supplemental treatment. CONCLUSIONS: Although the PDS Q24W effectively maintains vision and retinal stability in most eyes with nAMD, a small proportion of patients with features of difficult-to-treat nAMD may benefit from supplemental intravitreal anti-VEGF injections and initial close monitoring is recommended.

Unusual Artifacts Encountered during Routine Studies on Positron Emission Tomography-Computed Tomography and Gamma Camera.

Artifacts in nuclear medicine imaging are not uncommon. We are aware of some of these, for which we follow necessary protocols to avoid them. However, there are some unusual and unavoidable artifacts that we come across in daily imaging, which may be of concern and need to be detected and corrected on time. Hence, sharing a few such unusual artifacts we encountered while performing routine studies on positron emission tomography-computed tomography and gamma cameras, evaluating the cause and possible precautions.

Evaluation of pharmacist-led transition of care program in patients with acute coronary syndrome.

BACKGROUND: Guideline-directed medical therapies (GDMTs), initiated in-hospital and continued during the transition to outpatient care, are paramount to successful outcomes for patients with acute coronary syndrome (ACS). Incomplete discharge medication prescribing and delayed follow-up lead to worse cardiovascular outcomes. OBJECTIVES: We investigated a system of care using inpatient and outpatient clinical pharmacists to close GDMT gaps, ensure seamless transition to outpatient care, improve patient education, and optimize therapies. METHODS: We conducted a pre-post cohort analysis of patients with ACS pre- versus post-intervention to compare process metrics and key outcomes using electronic health record data. RESULTS: There were 181 and 135 patients in the pre- and post-intervention cohorts, respectively. Patients post-intervention were significantly more likely to have appropriately-timed follow-up visits scheduled with cardiology (79% vs. 51%, P < 0.0001) and primary care (57% vs. 43%, P = 0.01), to be discharged with prescriptions for P2Y12 inhibitors (87% vs. 64%, P < 0.0001), high dose statins (86% vs. 70%, P = 0.001), and beta blockers (87% vs. 76%, P = 0.01), and significantly less likely to have 30-day all-cause hospital readmissions (4% vs. 12%, P = 0.02) and emergency department (ED) visits (10% vs. 18%, P = 0.04). CONCLUSIONS: The integration of advanced practicing pharmacists into a cardiology team at transition and post-hospitalization resulted in improved rates of posthospital follow-up visits, optimization of GDMT medications, and significantly lower 30-day hospital readmission and ED utilization.

Small Intestinal Adenocarcinoma Involving a Submucosal Ectopic Lymph Node: A Case Report.

An 83-year-old male with a 55-year history of Crohn's disease, ileocecectomy 40 years prior, and naturopathic treatment for 25 years, presented with nausea, vomiting, and abdominal pain. Computed tomography of abdomen and pelvis demonstrated partial small intestinal obstruction and a 4.4-cm solid left renal mass. After 3 months of recurrent intestinal obstruction and development of a pericolonic abscess, resection of the ileocolonic anastomosis, abscess, and partial nephrectomy were performed. Histopathology demonstrated chronic active enteritis with fistula tract formation, consistent with Crohn's disease, and moderately differentiated small intestinal adenocarcinoma extending from mucosa into subserosa. A submucosal intestinal lymph node-like structure containing adenocarcinoma demonstrated endothelial venules, open marginal and intermediate sinuses, multiple polarized germinal centers, and partial capsule, consistent with an ectopic lymph node, also called a tertiary lymphoid organ. Twenty mesenteric lymph nodes were negative for carcinoma. The renal mass was a papillary renal cell carcinoma, Stage I. Intestinal tertiary lymphoid organs form in chronic immune activation and have variable structures ranging from simple B and T cell clusters to organized groups with high endothelial venules and lymphatic vessels. Encapsulation of tertiary lymphoid organs is rare, with some sources claiming this entity is never encapsulated. To our knowledge, this is the first report of small intestinal adenocarcinoma involving a submucosal encapsulated tertiary lymphoid organ, the prognostic significance of which is uncertain. We suggest increased awareness of intestinal tertiary lymphoid organs as an entity and further studies to delineate the effect their involvement by adenocarcinoma imparts on survival.

Evaluation of treatment response by Hopkins criteria on 18 F FDG PET-CT in patients of non-small cell lung cancer and its comparison with PERCIST response criteria.

AIM: To assess treatment response on FDG PET-CT in NSCLC patients by visual Hopkins score compared to PERCIST criteria and its potential for prognostication (or its correlation with survival). METHODS: Forty-four NSCLC patients with baseline and post-treatment FDG PET-CT scans were included, and interpreted using Hopkins and PERCIST criteria classifying patients into responders and non-responders. PERCIST-based CMR and PMR, and Hopkins Scores 1,2,3 were classified responders. PERCIST-based SD and PD and Hopkins scores 4,5 were classified as non-responders. Patients were followed upto 24 months after treatment completion. Cohen kappa for inter-criteria agreement and Kaplan Meir curve for overall survival (OS) analysis done. RESULTS: Out of 44 patients, PERCIST classified 27 (61.3%) as responders and 17 (38.6%) as non-responders, whereas Hopkins classified 12 patients (27.3%) as responders and 32 (72.7%) as non-responders. Inter-criteria agreement was low (kappa=0.19) with discordance in 45.5% of patients. Eighteen of 20 discordant cases were non-responders on Hopkins and responders on PERCIST, of which 88.8% were non-responders on follow-up as predicted by Hopkins. PERCIST responders had OS of 96.4% and 64.3% at 9 and 24 months, respectively, while non-responders OS was 93.5% and 40.2% at 9 and 24 months, respectively ( P -value = 0.049). However, responders on Hopkins had OS of 100% at 24 months, whereas non-responders had OS of 93.5% and 51.5% at 9 and 24 months, respectively ( P -value = 0.232). CONCLUSION: Semi-quantitative PERCIST and visual Hopkins criteria show low inter-criteria agreement, with visual criteria better-predicting survival in patients of NSCLC.

Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication.

With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation.

An Antimicrobial Fabric Using Nano-Herbal Encapsulation of Essential Oils.

Lab coats are widely used in biohazard laboratories and healthcare facilities as protective garments to prevent direct exposure to pathogens, spills, and burns. These cotton-based protective coats provide ideal conditions for microbial growth and attachment sites due to their porous nature, moisture-holding capacity, and retention of warmth from the user's body. Several studies have demonstrated the survival of pathogenic bacteria on hospital garments and lab coats, acting as vectors of microbial transmission. A common approach to fix these problems is the application of antimicrobial agents in textile finishing, but concerns have been raised due to the toxicity and environmental effects of many synthetic chemicals. The ongoing pandemic has also opened a window for the investigation of effective antimicrobials and eco-friendly and toxic-free formulations. This study uses two natural bioactive compounds, carvacrol and thymol, encapsulated in chitosan nanoparticles, which guarantee effective protection against four human pathogens with up to a 4-log reduction (99.99%). These pathogens are frequently detected in lab coats used in biohazard laboratories. The treated fabrics also resisted up to 10 wash cycles with 90% microbial reduction, which is sufficient for the intended use. We made modifications to the existing standard fabric tests to better represent the typical scenarios of lab coat usage. These refinements allow for a more accurate evaluation of the effectiveness of antimicrobial lab coats and for the simulation of the fate of any accidental microbial spills that must be neutralized within a short time. Further studies are recommended to investigate the accumulation of pathogens over time on antimicrobial lab coats compared to regular protective coats.

18 F-FDG PET-CT Evaluation of Primary Adrenal Ewing Sarcoma with Venous Thrombosis: An Unusual Presentation.

Ewing sarcoma (EWS) is primarily an osseous malignancy of childhood and young adults. Extraskeletal occurrence is less frequent and primary adrenal involvement is an even rare presentation. We present such a case of a 7-year-old boy diagnosed with adrenal EWS with associated venous thrombosis and pulmonary embolism detected on 18 F-fluorodeoxyglucose positron emission tomography-computed tomography scan.

Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen.

The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-ß. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry.

Mimicker of Osteoblastic Skeletal Metastasis on 18 F-FDG PET/CT Scan in a Case of Primary Mediastinal Germ Cell Tumor.

ABSTRACT: Primary mediastinal germ cell tumors are uncommon tumors, of which the nonseminomatous type is more likely to metastasize than the seminomatous type. Primary mediastinal germ cell tumors may also present with superior vena cava obstruction. Here, we present this case of primary mediastinal germ cell tumor with superior vena cava obstruction causing dilatation of collaterals in dorsal intravertebral venous plexus, which strongly mimics sclerotic skeletal lesions/metastasis on a Contrast-enhanced CT scan and also appears FDG avid on PET scan. Herein, we can differentiate the two by just a simple review of plain CT scan image.

Multigenerational diabetes mellitus.

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, "developmental programming", has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.

Role of 18F-FDG PET/CT for detection of recurrence and metastases in renal cell carcinoma-are we underusing PET/CT?

PURPOSE The aim of this study was to compare 18F-fluorodeoxyglucose positron emission tomography- computed tomography (18F-FDG PET/CT) scan with computed tomography (CT) scan for detecting recurrence and metastasis in renal cell carcinoma patients. METHODS This retrospective study included patients from October 2013 to April 2017. Contrast-enhanced CT and PET/CT scans were compared and correlated with histopathology or/and follow-up studies. RESULTS Seventy-six patients, 60 males, were included. Lesions included primary renal, recurrent renal fossa lesions, lymph nodes, and distant metastatic lesions. Of 176 malignant lesions, CT detected 157 lesions; of which, 154 were true positive. Twenty-two false-negative lesions showed abnormal FDG uptake. CT scan had positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and accuracy of 98.0%, 37.1%, 87.5%, 81.2%, and 86.9%, respectively. All 176 lesions were PET/CT-positive. PET/CT had PPV, NPV, sensitivity, specificity, and accuracy of 100% each. The specificity and NPV of PET/CT were superior (P < .05). CONCLUSION PET/CT appears more accurate than CT scan for detecting metastasis and recurrence in renal cell carcinoma patients.

SARS-CoV-2 variant spike and accessory gene mutations alter pathogenesis.

The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the spike protein. Although these differences in spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome that may also affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through interference with innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other nonspike mutations on SARS-CoV-2 pathogenesis, we synthesized both viruses possessing deletions in the accessory genes as well as viruses where the WA-1 spike is replaced by each variant spike gene in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to both WA-1 and the full variant viruses. Our work has revealed that the accessory proteins contribute to SARS-CoV-2 pathogenesis and the nonspike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host. This work suggests that while spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may alter clinical disease presentation.

Post-COVID-19 Unusual Inflammatory Syndromes Detected on 18F-FDG PET/CT Scan.

ABSTRACT: SARS-CoV-2 is primarily known to cause respiratory symptoms. However, in this global COVID-19 pandemic, we have come across many extrapulmonary manifestations during and in the immediate post-COVID phase such as gastrointestinal symptoms, kidney and liver injury, myocardial dysfunction and acute coronary syndromes, and neurological, thromboembolic, dermatological, and musculoskeletal disorders. We present 2 such unusual cases of post-COVID complications-diffuse panniculitis and inflammatory myositis, as well as their clinical and FDG PET/CT imaging features.

Recurrent gestational diabetes : Breaking the transgenerational cycle with lifestyle modification.

PURPOSE: This literature review is aimed at examining the benefits of lifestyle modifications in preventing recurrent gestational diabetes (GDM). Worldwide GDM affects approximately 16.2% of all pregnancies with significant maternal, fetal and neonatal complications. Almost two thirds of pregnant women with GDM will develop type 2 diabetes mellitus (T2DM) in the years following pregnancy. The proportion of women affected by GDM is on the rise and reflects increasing trends in T2DM as well as adult and childhood obesity. METHODS: Using predefined subject headings, we searched for relevant articles from the PubMed, Scopus, and Cochrane databases. RESULTS: For high-risk women lifestyle modifications, such as dietary and exercise changes, are the mainstay of treatment to reduce negative outcomes for both women and their pregnancies. This includes reducing the incidence of recurrent GDM and future T2DM by intervening during pregnancy and in the postnatal period. CONCLUSION: This review provides an overview of the literature to date, discusses different targeted approaches and how these interventions can optimise their benefits, and where further research is required.

Incidental Detection of Mandibular Metastasis in Renal Cell Carcinoma on 99mTc-MIBI Scan.

ABSTRACT: MIBI scintigraphy is the most widely used modality to identify parathyroid adenomas preoperatively. However, MIBI is also known to accumulate in multiple benign and malignant lesions. In renal cell carcinoma, 30% of the patients present with distant metastasis, commonly lungs and bone; however, jaw bone metastases are extremely rare (<1% of oral malignancies). Here we present a rare case of MIBI-avid mandibular metastasis in bilateral renal cell carcinoma on 99mTc-MIBI scintigraphy. Thus, we emphasize on careful interpretation of 99mTc-MIBI scans, which in addition to parathyroid adenomas can incidentally detect concurrent malignant lesions.

Role of 18F-Fluorodeoxyglucose Positron Emission Tomography-Contrast-Enhanced Computed Tomography in Detection of Early Recurrence with Peritoneal Disease in a Case of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is an uncommon and highly aggressive malignancy with a poor prognosis. Common sites of metastasis are lung, liver, and lymph nodes. We present a case of ACC in a 54-year-old female with an early disease recurrence of unusual hypervascular peritoneal metastatic abdominal-pelvic deposits detected on 18F-fluorodeoxyglucose positron emission tomography-contrast-enhanced computed tomography scan.

An Unusual Case of Urothelial Carcinoma of Bladder with Metastasis to Brain and Skeletal Muscles Evaluated on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Urothelial or transitional cell carcinoma is the most prevalent variant of urinary bladder carcinoma worldwide occurring in both men and women. There are a very few cases described in the literature with metastasis to skeletal muscles and even fewer cases with metastatic site in the brain. We present a case of high-grade urothelial carcinoma with metastasis to the left temporal lobe as well as multiple inter- and intra-muscular deposits in the left thigh.

Can 18F-FDG PET/CT alone or combined with radiology be used to reliably grade cartilage bone neoplasms for surgical decision making?

OBJECTIVE: Treatment of chondrosarcomas is grade based; intralesional curettage for grade 1 and resection for grade 2 or more. Currently used methods to determine grades before surgery are not highly accurate and create a dilemma for the surgeon. We have used a PET-CT combined with imaging to answer the following study questions: (1) Does SUVmax value from an 18F-FDG PET/CT correlate with the grade of chondrosarcoma? (2) Can a cutoff SUVmax value be used to differentiate between various grades of chondroid neoplasms with sufficient sensitivity and specificity? (3) Does SUVmax guide the clinician and add value to radiology in offering histologic grade-dependent management? METHODS: SUVmax values of patients with suspected chondrosarcoma were retrospectively correlated with the final histology grade for the operated patients. Radiologic parameters and radiology aggressiveness scores (RAS) were reevaluated and tabulated. RESULTS: Totally 104 patients with chondroid tumors underwent 18F-FDG PET/CT assessment. In total 73 had tissue diagnosis available as a pretreatment investigation. Spearman correlation indicated that there was a significant positive association between SUVmax and the final histology grading of chondroid tumors (correlation coefficient = 0.743; P < 0.01). SUVmax cutoff of 13.3 was 88.9% sensitive and 100% specific for diagnosing dedifferentiated chondrosarcomas. An RAS cutoff value of 3 or more could diagnose IHGCS with a sensitivity of 80.7% and specificity of 93.75%. Adding an SUVmax cutoff of 3.6 improves the sensitivity to 89.5%. CONCLUSION: SUVmax value can reliably help diagnose dedifferentiated chondrosarcoma and when added to the radiology score can improve the accuracy of grading chondrosarcoma.

An Unusual Case of Bilateral Ureteric Metastasis on PSMA PET-CT Scan in Carcinoma Prostate.

ABSTRACT: The most common locations for metastasis in adenocarcinoma of the prostate gland are lymph nodes, bone, lung, and liver. The involvement of the ureter as a site of metastasis in prostate carcinoma is quite rare in literature. Here we present a case involving bilateral ureters along with bilateral vesicoureteric junctions in a known case of prostate adenocarcinoma.