Monocyte Production of C1q Potentiates CD8+ T Cell Function Following Respiratory Viral Infection.

Respiratory viral infections remain a leading cause of morbidity and mortality. Using a murine model of human metapneumovirus (HMPV), we identified recruitment of a C1q-expressing inflammatory monocyte population concomitant with viral clearance by adaptive immune cells. Genetic ablation of C1q led to reduced CD8+ T cell function. Production of C1q by a myeloid lineage was necessary to enhance CD8+ T cell function. Activated and dividing CD8+ T cells expressed a C1q receptor, gC1qR. Perturbation of gC1qR signaling led to altered CD8+ T cell IFN-γ production, metabolic capacity, and cell proliferation. Autopsy specimens from fatal respiratory viral infections in children demonstrated diffuse production of C1q by an interstitial population. Humans with severe COVID-19 infection also demonstrated upregulation of gC1qR on activated and rapidly dividing CD8+ T cells. Collectively, these studies implicate C1q production from monocytes as a critical regulator of CD8+ T cell function following respiratory viral infection. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Management of Idiopathic Infantile Chylous Ascites.

Chylous ascites is the accumulation of triglyceride-rich lymphatic fluid in the peritoneal cavity. We present the case of a four-month-old male admitted for abdominal distension. A large volume of ascites was confirmed by imaging. Paracentesis indicated chylous aspirate and drainage was performed using a pigtail catheter. Total parenteral nutrition was initiated and fluconazole prophylaxis was implemented for seven days. Twenty-six days after admission, abdominopelvic magnetic resonance imaging showed trace ascites but no signs of lymphatic malformation. He began transitioning to nasogastric feeds with plans to eventually resume oral feeds. This case not only highlights the limitations in our abilities to definitively identify the etiology of pediatric chylous ascites but also demonstrates how chylous ascites management can carefully combine conservative and surgical strategies to optimize patient outcomes.

STAT1 Employs Myeloid Cell-Extrinsic Mechanisms to Regulate the Neutrophil Response and Provide Protection against Invasive Klebsiella pneumoniae Lung Infection.

Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread bacterial dissemination and lung injury development. Yet, myeloid cell STAT1 was dispensable for control of KP proliferation and dissemination, because myeloid cell-specific STAT1-deficient (LysMCre/WT;Stat1fl/fl) mice showed bacterial burden in the lung, liver, and kidney similar to that of their wild-type littermates. Surprisingly, IL-17-producing CD4+ T cells infiltrated Stat1-/- murine lungs early during KP infection. The increase in Th17 cells in the lung was not due to preexisting immunity against KP and was consistent with circulating rather than tissue-resident CD4+ T cells. However, blocking global IL-17 signaling with anti-IL-17RC administration led to increased proliferation and dissemination of KP, suggesting that IL-17 provided by other innate immune cells is essential in defense against KP. Contrastingly, depletion of CD4+ T cells reduced Stat1-/- murine lung bacterial burden, indicating that early CD4+ T cell activation in the setting of global STAT1 deficiency is pathogenic. Altogether, our findings suggest that STAT1 employs myeloid cell-extrinsic mechanisms to regulate neutrophil responses and provides protection against invasive KP by restricting nonspecific CD4+ T cell activation and immunopathology in the lung.

Scleroderma after COVID-19 Infection and Vaccination.

Scleroderma is a rare autoimmune connective tissue disorder characterized by fibrotic hardening and tightening of the skin. Scleroderma develops as a drug-induced and paraneoplastic phenomenon; however, scleroderma associated with COVID-19 has been rarely discussed. We present an updated review of scleroderma after the COVID-19 infection and vaccination. Literature searches were conducted on MEDLINE (PubMed), Embase, Scopus, and Google Scholar from 2019 to January 2023. In all, 13 studies were selected based on the subject relevance, with screening of references contained in the selected papers. As of January 2023, we had four patients with scleroderma after the COVID-19 infection (Mage = 54.50 years; Rage = 47-61 years; man-woman ratio = 1:3) and 10 patients with scleroderma after the COVID-19 vaccination (Mage = 62.8 years; Rage = 45-73 years; man-woman ratio = 1:9). Moderna's Spikevax accounted for two patients, Pfizer-BioNTech's Tozinameran accounted for seven patients, and Oxford-Astra Zeneca's Vaxzevria accounted for one patient. Hypotheses for the pathogenesis of scleroderma after the COVID-19 infection and vaccination included molecular mimicry, cytokine activation, and endothelial injury. Although the benefits of the COVID-19 vaccines still outweigh the risks, we advise clinicians to monitor for this rare potential complication.

Advanced thallium toxicity.

Thallium is a highly toxic tasteless, odourless and water-soluble metal that can be absorbed through the skin, inhaled or ingested. Due to the rarity of thallium toxicity, it is frequently misdiagnosed or the diagnosis is delayed. We report a 41-year-old male landscaper admitted for acute polyneuropathy and abdominal pain. He was treated for suspected Guillain-Barré syndrome and later autoimmune encephalopathy. However, over the next 42 days, he developed worsening muscle weakness, delirium and alopecia, and was diagnosed with thallium toxicity. After combining Prussian blue, activated charcoal and continuous venovenous haemofiltration, he improved though with neuropsychiatric and neuromuscular sequelae. We highlight the need to manage information disclosure properly and to preserve evidence, when the source of a toxin is unclear.

Toxic epidermal necrolysis and Stevens-Johnson syndrome after COVID-19 infection and vaccination.

Stevens-Johnson Syndrome (SJS) is a rare but severe skin reaction characterized by blistering and peeling of the skin and ulcerations of mucous membranes; toxic epidermal necrolysis (TEN) is a subset of SJS characterized by the involvement of >30% of the skin. Though previously associated with drugs and infections, discussions on the association between TEN/SJS and COVID-19 have been limited. We present a review of TEN/SJS after COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 8/2022. Thirty-eight articles were selected based on subject relevance, and references within selected articles were also screened for relevance. As of 8/2022, there have been 34 published cases of TEN, SJS, and SJS-TEN overlap after COVID-19 infection and vaccination, including 12 cases after vaccination and 22 cases after infection. Multiple authors hypothesize that virotopes or excipients in COVID-19 vaccines can activate T-cells or cytokines to induce TEN/SJS. Meanwhile, some hypothesize that COVID-19 infection induces immune activation that can trigger TEN/SJS or increase susceptibility to drug-induced TEN/SJS. Treatments for post-infection and post-vaccination TEN/SJS vary significantly. We recommend remaining vigilant for this rare and severe potential complication.

Lichen planus after COVID-19 infection and vaccination.

Lichen planus (LP) is an inflammatory disorder believed to result from CD8 + cytotoxic T-cell (CTL)-mediated autoimmune reactions against basal keratinocytes. We present a review of LP following COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 7/2022. 36 articles were selected based on subject relevance, and references within articles were also screened. 39 cases of post-vaccination LP and 6 cases of post-infection LP were found among case reports and case series. 152 cases of post-vaccination LP and 12 cases of post-infection LP were found in retrospective and prospective studies. LP is a rare complication of COVID-19 infection and vaccination that may be mediated by overstimulation of T-cell responses and proinflammatory cytokine production. However, it does not represent a limitation against COVID-19 vaccination, and the benefits of vaccination considerably outweigh the risks.

Chylothorax After Schwannoma Resection.

Schwannomas are tumors derived from Schwann cells of the peripheral nerve sheath that are usually benign; nonetheless, they can cause significant morbidity. When indicated, surgical resection is the gold standard of treatment for schwannomas. However, chylothorax is a rare postoperative complication of thoracic surgery. We present a case of chylothorax after thoracic schwannoma resection. A 61-year-old woman underwent a computed tomography (CT) scan for suspected nephrolithiasis, which instead found a right mediastinal mass that was confirmed to have features consistent with a schwannoma on thoracic spine magnetic resonance imaging (MRI). Right thoracotomy and schwannoma resection were performed, resulting in the complete removal of the schwannoma without capsular invasion. Two chest tubes were also inserted. On postoperative day 1 (POD1), the patient presented with a chylothorax that was initially treated with chest tube suctioning and total parenteral nutrition (TPN). However, a repeat right thoracotomy with thoracic duct ligation and dry talc chemical pleurodesis was subsequently performed on POD15 due to a lack of clinical improvement, which saw the resolution of the chylothorax without recurrence. Chylothorax is a rare but severe postoperative complication of thoracic surgeries, including those that involve tumor resections. We present a case of chylothorax after thoracic schwannoma resection that initially failed conservative management but eventually resolved after thoracic duct ligation and chemical pleurodesis. This case highlights the need for effective non-surgical treatments for chylothorax, the importance of remaining vigilant for rare postoperative complications, and the need for randomized controlled trials (RCTs) to develop a standardized chylothorax management algorithm.

Left Ovarian Cyst With Overlying Sigmoid Colon.

Ovarian cysts are usually asymptomatic and self-resolvable, but large cysts can increase the risk of ovarian torsion or rupture and may be indicated for surgical intervention. We present the case of a large left ovarian cyst in which laparoscopic left salpingo-oophorectomy was challenged by an overlying sigmoid colon with dense adhesions. A 47-year-old female patient presented to the emergency department with abdominal pain in the right lower quadrant. Ultrasound and computed tomography scans found a large left ovarian cyst and multiple small right ovarian cysts. Due to the size of the left ovarian cyst increasing the risk for torsion, the patient was indicated for laparoscopic left salpingo-oophorectomy. However, the cyst was inaccessible due to the overlying sigmoid colon and dense adhesions on all sides. The surgeons elected to drain the cyst, and the patient was counseled that it was safe to monitor for postoperative recurrence over the next three months. Though laparoscopic surgery is considered a gold standard modality for minimally-invasive ovarian cystectomy/oophorectomy, our case illustrates how it can be challenging when treating left-sided adnexal masses in post-hysterectomy patients due to rectosigmoid and adhesional obstruction. In the context of this challenge, our case further demonstrates the importance of preoperative ovarian cancer screening and favoring conservative treatment options whenever possible.

Joint Hypermobility as a Potential Indicator of Marfan Syndrome and Ehlers-Danlos Syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder associated with the mutation of the FBN1 gene. Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders with similar clinical features to MFS that often requires genetic testing to confirm a diagnosis of an EDS subtype. MFS is diagnosed using the Ghent Nosology criteria, which screens for cardiovascular, musculoskeletal, integumentary, ocular, and pulmonary abnormalities. Though genetic testing has recently been increasingly emphasized in diagnosing MFS, it is not currently a mandatory component of the Ghent Nosology. We present the case of a nine-year-old male who presented with joint hypermobility of the shoulders, knees, and thumbs, and a family history of joint hypermobility in his 15-year-old brother. Genetic testing ruled out MFS, and the patient subsequently underwent testing for EDS, which further ruled out classical and hypermobile EDS. This case highlights the importance of supplementing the Ghent Nosology criteria with genetic testing in diagnosing MFS because it can aid in generating a differential diagnosis and optimizing diagnostic accuracy.

Exudative Retinal Detachment After ROP Laser Photocoagulation.

Exudative retinal detachment (ERD) can be a rare postoperative complication of laser photocoagulation surgery when used to treat type I retinopathy of prematurity (ROP). We present a case of bilateral ERD following ROP laser photocoagulation. A preterm male infant born at 24 weeks gestation and weighing 600 grams was diagnosed with stage 3/zone II/pre-plus ROP in both eyes. He was on oxygen therapy for 92 days due to chronic lung disease and was treated with laser photocoagulation at 40 weeks postmenstrual age. Initial laser settings (in use for over 15 years) were 300 mW power, 300 ms duration, and 300 ms intervals. Due to strong laser absorption, power was decreased to 250 mW for most of the procedure. He was prescribed prednisolone acetate drops four times per day for postoperative care. One week later, he developed complete ERD in both eyes. The patient was monitored in the neonatal intensive care unit (NICU) for three weeks and prednisolone acetate drops were increased to every two hours and tapered over one month. Complete resolution of ERD with residual peripheral exudate bilaterally was observed eight weeks after surgery. This case suggests that even after the settings of an ROP laser have been used safely for 15 years, it is important to tailor settings for each individual patient utilizing the least power and duration for laser application as possible. Furthermore, this case highlights the importance of titrating laser power in response to spot blanching throughout the procedure. However, near-complete resolution of post-ROP laser ERD is possible with minimal changes to standard postoperative management.