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.
Display omitted
•Airways show localized immune responses correlating to age and outcome in COVID-19•Airway T cells are activated and resident, while myeloid cells are hyperinflammatory•Aberrant CD163hi and HLA-DRlo monocytes predominate in COVID-19 blood•Monocytes infiltrate airways and lung alveoli potentially through a CCL2-CCR2 axis
Through longitudinal profiling of paired airways and blood from patients with severe COVID-19, Szabo et al. reveal airway immune responses that correlate with age and outcome. They further identify coordinate roles for T and myeloid cells in the respiratory tract and circulation in perpetuating lung pathology and disease pathogenesis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
Display omitted
•The human pancreas contains CD8+ TRMs exhibiting tissue-specific molecular signatures•Pancreas TRMs express high levels of PD-1 yet maintain strong effector function•During homeostasis, pancreas TRMs are regulated by PD-L1+ tissue macrophages•In chronic pancreatitis, TRM PD-1 levels and PD-L1+ macrophage density are reduced
Non-recirculating tissue-resident memory T cells (TRMs) mediate immune responses in non-lymphoid tissues. Using a human organ donor tissue resource, Weisberg et al. reveal that PD-1hi pancreas TRMs are regulated by PD-L1+ macrophages during homeostasis. Comparison with chronic pancreatitis patient samples shows how pancreas TRM regulation is altered during inflammation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Respiratory failure in COVID-19 is characterized by widespread disruption of the lung's alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and ...immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18-92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased peri-alveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there is also progressive loss of T2AE with increasing age which may increase susceptibility to COVID-19 mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that express distinctly high levels of T-cell activation and co-stimulation genes and strongly correlate with increased extent of alveolar epithelial cell depletion and CD8 T-cell cytotoxicity. Together, our results show that T2AE deficiency may underlie age-related COVID-19 risk and initiate alveolar injury shortly after infection; and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of lethal COVID-19.
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.
Three patients complained of significant flank pain were scheduled for percutaneous nephrolithotomy under general anesthesia in the prone position.
Patients were diagnosed with large renal calculi.
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.
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.
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.
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.
A 75-year-old woman in accelerated-phase chronic myeloid leukemia with hyperleukocytosis presented with acute respiratory distress syndrome. Despite early and aggressive pulmonary support and ...cytoreductive chemotherapy, the patient died. Autopsy confirmed the presence of the leukostasis syndrome. The clinical, radiologic, pathophysiologic, and therapeutic aspects of this entity are reviewed.
PDF
