A Systematic Review of Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis Following Coronavirus Disease 2019 Vaccination: A 2024 Update.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood vessels in the kidney, leading to renal impairment and potentially irreversible damage. Concerns have been raised over the reports of myeloperoxidase/perinuclear (MPO/p) ANCA GN following the coronavirus disease 2019 (COVID-19) vaccination. Our study provides a comprehensive insight into perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) GN after COVID-19 vaccination. We conducted a comprehensive literature search on PubMed, Cochrane Library, and EMBASE using the Medical Subject Headings (MeSH) terms related to "covid-19 vaccine," "glomerulonephritis," "p-ANCA," and "MPO-ANCA" up to March 5, 2024, to include cases of p-ANCA-associated GN following COVID-19 vaccination. Of the 4,102 articles, we included 29, reporting 35 patients demonstrating COVID-19 vaccine-induced p-ANCA GN, with 23 (65.7%) females and a median age of 69 years (mean ± SD = 63.22 ± 16). Twenty-six (74.28%) patients received the mRNA vaccine (Pfizer = 19, Moderna = 7). Seventeen (48.57%) patients presented with p-ANCA GN after the second dose of the COVID-19 vaccine, with a median gap of 19 days (1-84 days). Constitutional symptoms (54.28%) and acute kidney injury (42.85%) were the most reported initial presentations, and elevated serum creatinine (mean peak serum creatinine = 4.98 ± 5.02 mg/dL), hematuria, and proteinuria were the laboratory findings. MPO/p-ANCA was positive in 31 (88.6%) patients. All patients underwent renal biopsy, and crescentic GN was the most common finding among 27 (77.14%) patients. Management of p-ANCA GN included steroids in 30 (85.71%) patients, followed by rituximab (28.57%), and plasmapheresis (22.86%). Most patients responded well to treatment, with complete remission in 29 (82.86%) and relapse in four (11.42%) patients. Two patients did not achieve remission and became dialysis dependent. ANCA-associated GN is a rare and life-threatening complication of the COVID-19 vaccine, necessitating urgent evaluation and management. COVID-19 vaccine-induced p-ANCA GN should be included in the differential diagnoses of patients presenting with kidney injury after vaccination.

Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.

PURPOSE OF REVIEW: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain. RECENT FINDINGS: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

Liquid biopsy in the setting of leptomeningeal metastases: a systematic review and meta-analysis.

PURPOSE: The blood-brain barrier can prevent circulating tumor DNA (ctDNA) derived from the central nervous system from entering the blood making it challenging to evaluate molecular features of leptomeningeal metastasis (LM). Accordingly, we sought to systematically compare the diagnostic power or significance of ctDNA derived from cerebrospinal fluid (CSF) compared to plasma ctDNA in patients with LM. METHODS: A systematic review and meta-analysis was performed under the PRISMA guideline. We used PubMed, EMBASE, and the EuroPMC to search the literature using combinations of the following terms: circulating tumor DNA, ctDNA, circulating tumor cell, brain metastasis, leptomeningeal metastasis, outcome(s), and prognosis. We included all available English language studies that compared the diagnostic significance of CSF derived and serum ctDNA. All eligible studies level of bias was assessed using the New Castle Ottawa Scale (NOS). RESULTS: Our meta-analysis from 6 included studies (n = 226) that confirmed the diagnostic power of liquid biopsies in detecting genomic alteration is better when taking a CSF-derived samples than from the plasma (RR 1.46 [0.93; 2.29]; I2 = 92%; p-value < 0.01). CONCLUSION: CSF ctDNA is better at describing molecular landscape for LM; such an understanding may ultimately help inform patient treatment and responses to therapy.

Long-term exposure of the binary mixture of cadmium and mercury damages the developed ovary of adult zebrafish.

The toxicity of the binary mixture of cadmium (Cd) and mercury (Hg) on the ovary of adult zebrafish was evaluated in the present study. Adult female zebrafish were exposed to cadmium chloride (1 mg/L), mercury chloride (30 µg/L), and a binary mixture of both metals for 21 days. The toxic effects of both metals on the ovary were investigated by evaluating the oxidative stress markers and related gene expression in ovarian tissue along with the histopathological examination. The significantly decreased level of GSH and increased level of MDA in ovarian tissue of adult female zebrafish exposed to Cd + Hg indicated that the exposure of binary mixture of Cd and Hg caused more lipid peroxidation in the ovary. The significant changes in expression of mRNA of catalase (CAT) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) were not observed in the ovary of zebrafish exposed to the binary mixture. Upon histological evaluation, a decreased number of full-growth (mature) oocytes along with degenerative changes due to Cd exposure were noticed, while ovary of zebrafish of the Hg-exposed group had shown a decreased number of pre-and early vitellogenic oocytes along with atretic previtellogenic oocytes compared to the control group. The ovary of zebrafish of the Cd + Hg-exposed group had shown a decreased number of previtellogenic oocytes with marked pathological changes in mature oocytes. Present findings elucidate that simultaneous long-term exposure of Cd and Hg compared to individual exposure significantly damaged the various stages of oocytes of an ovary of adult zebrafish.

Cancer-Causative Mutations Occurring in Early Embryogenesis.

Mosaic mutations in normal tissues can occur early in embryogenesis and be associated with hereditary cancer syndromes when affecting cancer susceptibility genes (CSG). Their contribution to apparently sporadic cancers is currently unknown. Analysis of paired tumor/blood sequencing data of 35,310 patients with cancer revealed 36 pathogenic mosaic variants affecting CSGs, most of which were not detected by prior clinical genetic testing. These CSG mosaic variants were consistently detected at varying variant allelic fractions in microdissected normal tissues (n = 48) from distinct embryonic lineages in all individuals tested, indicating their early embryonic origin, likely prior to gastrulation, and likely asymmetrical propagation. Tumor-specific biallelic inactivation of the CSG affected by a mosaic variant was observed in 91.7% (33/36) of cases, and tumors displayed the hallmark pathologic and/or genomic features of inactivation of the respective CSGs, establishing a causal link between CSG mosaic variants arising in early embryogenesis and the development of apparently sporadic cancers. SIGNIFICANCE: Here, we demonstrate that mosaic variants in CSGs arising in early embryogenesis contribute to the oncogenesis of seemingly sporadic cancers. These variants can be systematically detected through the analysis of tumor/normal sequencing data, and their detection may affect therapeutic decisions as well as prophylactic measures for patients and their offspring. See related commentary by Liggett and Sankaran, p. 889. This article is highlighted in the In This Issue feature, p. 873.

Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression.

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.

Comparison of ReLEx SMILE and PRK in terms of visual and refractive outcomes for the correction of low myopia.

PURPOSE: To compare the objective and subjective quality of vision after femtosecond laser-assisted small incision lenticule extraction (SMILE) and photorefractive keratectomy (PRK) for low myopia. METHODS: One hundred and twenty eyes from 60 patients (34 females, 26 males) undergoing bilateral correction of low myopia (≤-4 D SE) with either ReLEx SMILE or PRK were included. Visual acuity, contrast sensitivity and higher-order aberrations were recorded preoperatively and compared postoperatively. A quality of vision questionnaire was scored and analyzed 3 months postoperatively. RESULTS: At 3 months, the SMILE group had significantly better uncorrected and corrected distant visual acuity (CDVA), compared to PRK group (p = 0.01). Post-op spherical equivalent (SE) was comparable in both groups (SMILE = -0.15 ± 0.19 D, PRK = -0.14 ± 0.23 D, p = 0.72). However, SE predictability was better in SMILE group with 97% eyes within ±0.05 D compared to 93% eyes in the PRK group. Total higher-order aberrations (HOAs) were significantly higher in PRK compared to the SMILE group (p = 0.022). The SMILE group demonstrated slightly better contrast sensitivity, which was significant at spatial frequency of 12 cpd (p = 0.03). Four eyes in the PRK group had loss of CDVA by one line due to mild haze. CONCLUSIONS: Both SMILE and PRK were effective procedures for correction of low myopia. However, SMILE offered superior quality of vision and patient satisfaction due to better postoperative comfort and lower induction of aberrations at 3 months.

OcularTrauma Score: a useful predictor of visual outcome at six weeks in patients with traumatic cataract.

OBJECTIVE: To validate the predictive value of the Ocular Trauma Score (OTS) in injury cases with traumatic cataracts. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 787 eyes. METHODS: A total of 787 eyes of 787 subjects with traumatic cataracts were enrolled using specific inclusion criteria. The eyes were examined to review comorbidities caused by trauma. Surgery was performed for traumatic cataracts, lenses were implanted, and patients were treated for amblyopia, as applicable. The patients were reexamined 6 weeks postoperatively. On the basis of ocular trauma described according to the Birmingham Eye Trauma Terminology System, the patients were divided into 2 traumatic cataract groups: open globe injury and closed globe injury. The relationship of visual acuity (VA) with demographic and clinical variables was analyzed. The visual outcomes were predicted using the OTS, and the predictions were compared with the actual outcomes using statistical tests. MAIN OUTCOME MEASURES: Visual acuity. RESULTS: At 6 weeks postoperatively, 245 eyes (31%) had a VA ≥ 20/40 and 480 eyes (61.0%) had a VA >20/200. The OTS prediction was not significantly different when compared with actual visual outcome at 6 weeks postoperatively in all OTS categories. CONCLUSIONS: The relationship of VA at 6 weeks with demographic and clinical variables was analyzed. In this study, the OTS was found as a reliable tool to predict visual outcome in cases of traumatic cataracts 6 weeks postoperatively.

Comparative study of final visual outcome between open- and closed-globe injuries following surgical treatment of traumatic cataract.

OBJECTIVE: The objective of this work is to compare final visual outcomes in cases of surgically treated traumatic cataract between open-globe and closed-globe groups, as classified by the Birmingham Eye Trauma Terminology system. DESIGN: Observational cohort study. SETTING: Tertiary eye-care center at the trijunction of Gujarat, Madhya Pradesh, and Rajasthan states in central western India. METHODS: We enrolled patients meeting specific inclusion criteria, examined their eyes to review any co-morbidities due to trauma, performed surgery for traumatic cataracts, and implanted lenses. The patients were re-examined 6 weeks postoperatively. We classified the cases of traumatic cataract as either open-globe (group 1) or closed-globe (group 2), according to the Birmingham Eye Trauma Terminology (BETT) system, and compared visual acuity. OUTCOME MEASURES: Visual Acuity. RESULTS: Our cohort of 687 eyes with traumatic cataracts included 496 eyes in group 1 and 191 in group 2. Six weeks postoperatively, the visual acuity was >20/60 in 298 (58%) and 75 (39.1%) operated eyes in groups 1 and 2, respectively (p < 0.001, ANOVA). At follow-up, >20/60 vision was significantly higher in group 1 than in group 2 (OR = 1.61; 95% CI, 0.85-3.02). Overall, 373 eyes (54.3%) regained final visual acuity >20/60. CONCLUSIONS: Open-globe injury has a more favorable prognosis for satisfactory (>20/60) visual recovery after management of traumatic cataracts.