Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19.

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract.

Erector spinae plane block with catheter for management of percutaneous nephrolithotomy: A three case report.

INTRODUCTION: Percutaneous nephrolithotomy is a procedure used for management of refractory renal calculi. Oral and parenteral opioids, along with local anesthetic infiltration, neuraxial anesthesia, and paravertebral blocks are the most common methods of managing intra-operative and post-operative pain for these patients. The erector spinae plane block with catheter (ESPC) is a newer interfascial regional anesthetic technique that can be used to manage peri-operative pain in these patients. CLINICAL FINDINGS: Three patients complained of significant flank pain were scheduled for percutaneous nephrolithotomy under general anesthesia in the prone position. DIAGNOSES: Patients were diagnosed with large renal calculi. THERAPEUTIC INTERVENTIONS: Patients received ESPC in the pre-operative holding area at the level of the T7 transverse process. The ESPCS were bolused with a solution of 30 mL 0.25% bupivacaine with 4 mg dexamethasone prior to surgery. Patients also received oral tramadol 50 mg and acetaminophen 1 g as part of the multimodal pain protocol prior to surgery. After the procedure, the patients were bolused with 0.25% bupivacaine or started on an infusion of 0.25% bupivacaine to manage their pain. OUTCOMES: No opioid or other pain medications, other than the local anesthetic solution given in the ESPCs, were used during the intra-operative or post-operative period for management of pain in these patients. Visual analogue scale (VAS) scores were below 4 for all patients in the post-operative period, and patients did not report any issues with post-operative nausea or vomiting. CONCLUSION: These patients were compared to 3 prior patients who had undergone percutaneous nephrolithotomy without ESPC. The 3 patients without ESPC placement reported increased VAS scores, had increased opioid/pain medication consumption intraoperatively and postoperatively, and had increased incidence of perioperative nausea when compared to our ESPC patients. Our report shows that ESPC, in combination with a multimodal pain protocol, can be a good option for management of patients undergoing percutaneous nephrolithotomy.

Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway.

Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for TRM in maintaining immune homeostasis in the human pancreas through interactions with resident macrophages and the PD-1/PD-L1 inhibitory pathway. Using tissues obtained from organ donors, we identify that pancreas T cells comprise CD8+PD-1hi TRMs, which are phenotypically, functionally, and transcriptionally distinct compared to TRMs in neighboring jejunum and lymph node sites. Pancreas TRMs cluster with resident macrophages throughout the exocrine areas; TRM effector functions are enhanced by macrophage-derived co-stimulation and attenuated by the PD-1/PD-L1 pathways. Conversely, in samples from chronic pancreatitis, TRMs exhibit reduced PD-1 expression and reduced interactions with macrophages. These findings suggest important roles for PD-1 and TRM-macrophage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies.

Routine colonoscopy, diabetic eye care, mammogram and pap smear screening in vascular surgery patients.

Objective An increasing emphasis on preventive medicine has been supported by the recent reforms in United States health care system. Majority of the patients seen in vascular surgery clinics are elderly with more extensive medical comorbidities compared to the general population. Thus, these patients would be expected at higher risk for common malignant pathologies such as colon, breast and cervical cancer, and nonmalignant diseases such as diabetic retinopathy. This study looked at the screening compliance of vascular patients compared to data provided by Centers for Disease Control on the national and state levels. Methods The office records of 851 consecutive patients seen in Brooklyn and Staten Island vascular clinics were examined. We queried patients regarding their last colonoscopy, diabetic eye exams, recent mammograms, and Pap smears. Our patient screening compliance was compared between the two clinics as well as to the national and New York state data provided by Centers for Disease Control. Compliance with regard to patient's age was also examined. Results Patients referred to the Staten Island office have a better colonoscopy compliance compared to the Brooklyn office ( P = .0001) and the national Centers for Disease Control average ( P = .026). Compliance for mammography and cervical cancer screening was higher in Staten Island office compared to the Brooklyn office ( P = .0001, P < .0001), respectively. Compliance was lower for Pap smear ( P = .0273) in Brooklyn when compared to the national average. Compliance for colonoscopy increased with age for both clinics ( P = .001, P < .001), while Pap smear decreased ( P < .001, P = .004). Conclusion Patients in vascular clinics in an urban setting had better adherence to screening protocol than the national and state average, with the exception of female patients for colonoscopy in our Brooklyn vascular office. There exists variability in both patient populations based on sub-specific locality and demographics including socioeconomic status. Overall, however patients in Staten Island had better compliance and adherence to the screening protocol than Brooklyn vascular clinic.