Immune-related adverse kidney events by immune checkpoint inhibitors; a narrative review on current studies

Chemotherapy-associated renal injury is considered one of the major concerns among nephrological and oncological practice. The use of novel anti-neoplastic therapies that target carcinomas has helped in the detection of this form of renal injury. Immune checkpoint inhibitors (ICPIs) are a group of monoclonal antibodies targeting inhibitory receptors that exist on tumor cells and T cells. ICPIs are able to suppress tumors that might have escaped from the immune surveillance. Meanwhile, although ICPIs have shown promising efficacy in cancer treatment, their immune-related side effects limit their widespread use in cancer therapy schedules. One of the major side effects limiting ICPIs' usage is nephrotoxicity. Glomerular disease, acute interstitial nephritis (AIN), and acute tubular necrosis (ATN) are considered different infusion-related adverse events. Infiltration of eosinophils, T lymphocytes, and plasma cells, as well as interstitial inflammation and edema, leading to acute tubulointerstitial nephritis (ATIN). It is conceivable that the rupture of self-tolerance by ICPIs induces an autoimmune reaction against some specific self-antigens in the organs including kidneys. The exact nature of the antigen is unclear; however, it is possible that it is found in the renal tubular cells, as indicated by a greater frequency of ATIN in kidney biopsies. The current review paper discusses the relationship between ICPIs therapy and kidney disorders or more specifically, their possible role in renal damage along with renal toxicity profile in the setting of ICPIs treatment

The Effect of Preoperative Oral Melatonin on Postoperative Pain after Lumbar Disc Surgery: A Double-Blinded Randomized Clinical Trial

BACKGROUND: Despite advances in surgical and anesthesiology techniques, many patients continue to experience postoperative pain after lumbar disc surgeries. The aim of this study was to investigate the effect of preoperative oral melatonin on the severity of postoperative pain after lumbar laminectomy/discectomy. METHODS: In this double blinded randomized controlled clinical trial 80 patients undergoing an elective mini-open microdiscectomy surgery at Imam Khomeini educational hospital in Sari, Iran, were selected and randomly assigned into one of four groups. Patients in group A, B, C, and D received 3, 5 and 10 mg melatonin or placebo tablets one hour before surgery, respectively. Using the visual analogue scale (VAS) the severity of pain, nausea and vomiting, pruritus, and use of narcotics were assessed immediately after surgery and before leaving the post-anesthesia care unit, 6, 12 and 24 hours postoperatively. RESULTS: In all three groups receiving melatonin at all three different doses, postoperative pain was significantly less than the placebo group (P<0.01). There were no statistically significant differences in postoperative pain level between the three groups receiving melatonin (P>0.05). The amount of opioid received by the patients within 24 hours after surgery had statistically significant differences within the groups (P=0.043, F=2.58). The results of post hoc analysis in terms of postoperative pain intensity showed statistically significant differences between the two groups receiving melatonin at a dose of 5 mg and the placebo group (P= 0.04). No serious side effects reported in four groups. CONCLUSION: The use of oral melatonin with a dose of 5 mg, 1 hour before the surgery as an inexpensive method can effectively reduce pain intensity as well as the amount opioid use after lumbar laminectomy and discectomy

The Ionizing Photon Production Efficiency (ξion\xi_{ion}) Of Lensed Dwarf Galaxies At z∼2z \sim 2

We measure the ionizing photon production efficiency ($\xi_{ion}$) of low-mass galaxies ($10^{7.8}$-$10^{9.8}$ $M_{\odot}$) at $1.4<z<2.7$, allowing us to better understand the contribution of dwarf galaxies to the ionizing background and cosmic reionization. We target galaxies that are magnified by the strong lensing galaxy clusters Abell 1689, MACS J0717, and MACS J1149. We utilize Keck/MOSFIRE spectra to measure optical nebular emission line fluxes and HST imaging to measure the rest-UV and rest-optical photometry. We present two methods of stacking. First, we take the average of the log(L$_{H\alpha}$ /L$_{UV}$) of galaxies in our sample to determine the typical log($\xi_{ion}$). Second, we take the logarithm of the total L$_{H\alpha}$ over the total L$_{UV}$. We prefer the latter as it provides the total ionizing UV luminosity density of galaxies when multiplied by the non-ionizing UV luminosity density from the UV luminosity function. log($\xi_{ion}$) calculated from the second method is $\sim$ 0.2 dex higher than the first method. We do not find any strong dependence between log($\xi_{ion}$) and stellar mass, M$_{UV}$ or UV spectral slope ($\beta$). We report a value of log($\xi_{ion}$) $\sim25.47\pm 0.09$ for our UV-complete sample ($-22<M_{UV}<-17.3$) and $\sim25.37\pm0.11$ for our mass-complete sample ($7.8<\log(M_*)<9.8)$. These values are consistent with measurements of more massive, more luminous galaxies in other high-redshift studies that use the same stacking technique. Our log($\xi_{ion}$) is $0.2-0.3$ dex higher than low-redshift galaxies of similar mass, indicating an evolution in the stellar properties, possibly due to metallicity, age, or the prevalence of binary stars. We also find a correlation between log($\xi_{ion}$) and the equivalent widths of H$\alpha$ and [OIII]$\lambda$5007 fluxes, confirming that these equivalent widths can be used to estimate $\xi_{ion}$.Comment: 16 pages, 6 figures, 1 table, Accepted in Ap

The Detection of [O III] λ4363 in a Lensed, Dwarf Galaxy at z = 2.59: Testing Metallicity Indicators and Scaling Relations at High Redshift and Low Mass

We present Keck/MOSFIRE (Multi-Object Spectrometer for InfraRed Exploration) and Keck/LRIS (Low Resolution Imaging Spectrometer) spectroscopy of A1689-217, a lensed (magnification ~7.9), star-forming (SFR ~ 16 M_☉ yr⁻¹), dwarf (log(M_★/M_☉) = 8.07–8.59) Lyα emitter (EW₀ ~ 138 Å) at z = 2.5918. Dwarf galaxies similar to A1689-217 are common at high redshift and likely responsible for reionization, yet few have been studied with detailed spectroscopy. We report a 4.2σ detection of the electron-temperature-sensitive [O iii] λ4363 emission line and use this line to directly measure an oxygen abundance of 12 + log(O/H) = 8.06 ± 0.12 (~1/4 Z_☉). A1689-217 is the lowest-mass galaxy at z > 2 with an [O iii] λ4363 detection. Using the rest-optical emission lines, we measure A1689-217's other nebular conditions, including electron temperature (T e ([O iii]) ~ 14,000 K), electron density (n e ~ 220 cm⁻³), and reddening (E(B-V) ~ 0.39). We study relations between strong-line ratios and direct metallicities with A1689-217 and other galaxies with [O iii] λ4363 detections at z ~ 0–3.1, showing that the locally calibrated, oxygen-based, strong-line relations are consistent from z ~ 0 to 3.1. We also show additional evidence that the O₃₂ versus R₂₃ excitation diagram can be utilized as a redshift-invariant, direct-metallicity-based, oxygen abundance diagnostic out to z ~ 3.1. From this excitation diagram and the strong-line ratio–metallicity plots, we observe that the ionization parameter at fixed O/H is consistent with no redshift evolution. Although A1689-217 is metal-rich for its M_★ and star formation rate, we find it to be consistent within the large scatter of the low-mass end of the fundamental metallicity relation

Risk factors associated with long covid syndrome: A retrospective study

Background: Recently, people have recognized the post-acute phase symptoms of the COVID-19. We investigated the long-term symptoms associated with COVID-19, (Long COVID Syndrome), and the risk factors associated with it. Methods: This was a retrospective observational study. All the consecutive adult patients referred to the healthcare facilities anywhere in Fars province from 19 February 2020 until 20 November 2020 were included. All the patients had a confirmed COVID-19 diagnosis. In a phone call to the patients, at least three months after their discharge from the hospital, we obtained their current information. The IBM SPSS Statistics (version 25.0) was used. Pearson Chi square, Fisher’s exact test, t test, and binary logistic regression analysis model were employed. A P value of less than 0.05 was considered to be significant. Results: In total, 4,681 patients were studied, 2915 of whom (62.3%) reported symptoms. The most common symptoms of long COVID syndrome were fatigue, exercise intolerance, walking intolerance, muscle pain, and shortness of breath. Women were more likely to experience long-term COVID syndrome than men (Odds Ratio: 1,268; 95% Confidence Interval: 1,122-1,432; P=0.0001), which was significant. Presentation with respiratory problems at the onset of illness was also significantly associated with long COVID syndrome (Odds Ratio: 1.425; 95% Confidence Interval: 1.177-1.724; P=0.0001). A shorter length of hospital stay was inversely associated with long COVID syndrome (Odds Ratio: 0.953; 95% Confidence Interval: 0.941-0.965; P=0.0001). Conclusion: Long COVID syndrome is a frequent and disabling condition and has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness

The Lyman Continuum Escape Fraction of Star-forming Galaxies at 2.4≲z≲3.72.4\lesssim z\lesssim3.7 from UVCANDELS

The UltraViolet Imaging of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey Fields (UVCANDELS) survey is a Hubble Space Telescope (HST) Cycle-26 Treasury Program, allocated in total 164 orbits of primary Wide-Field Camera 3 Ultraviolet and Visible light F275W imaging with coordinated parallel Advanced Camera for Surveys F435W imaging, on four of the five premier extragalactic survey fields: GOODS-N, GOODS-S, EGS, and COSMOS. We introduce this survey by presenting a thorough search for galaxies at $z\gtrsim2.4$ that leak significant Lyman continuum (LyC) radiation, as well as a stringent constraint on the LyC escape fraction ($f_{\rm esc}$) from stacking the UV images of a population of star-forming galaxies with secure redshifts. Our extensive search for LyC emission and stacking analysis benefit from the catalogs of high-quality spectroscopic redshifts compiled from archival ground-based data and HST slitless spectroscopy, carefully vetted by dedicated visual inspection efforts. We report a sample of five galaxies as individual LyC leaker candidates, showing $f_{\rm esc}^{\rm rel}\gtrsim60\%$ estimated using detailed Monte Carlo analysis of intergalactic medium attenuation. We develop a robust stacking method to apply to five samples of in total 85 non-detection galaxies in the redshift range of $z\in[2.4,3.7]$. Most stacks give tight 2-$\sigma$ upper limits below $f_{\rm esc}^{\rm rel}<6\%$. A stack for a subset of 32 emission-line galaxies shows tentative LyC leakage detected at 2.9-$\sigma$, indicating $f_{\rm esc}^{\rm rel}=5.7\%$ at $z\sim2.65$, supporting the key role of such galaxies in contributing to the cosmic reionization and maintaining the UV ionization background. These new F275W and F435W imaging mosaics from UVCANDELS have been made publicly available on the Barbara A. Mikulski Archive for Space Telescopes.Comment: 33 pages, 21 figures, and 5 tables. Resubmitted after addressing the referee repor

The Ultraviolet Luminosity Function at 0.6 < z < 1 from UVCANDELS

UVCANDELS is a Hubble Space Telescope Cycle-26 Treasury Program awarded 164 orbits of primary ultraviolet (UV) F275W imaging and coordinated parallel optical F435W imaging in four CANDELS fields—GOODS-N, GOODS-S, EGS, and COSMOS—covering a total area of ∼426 arcmin2. This is ∼2.7 times larger than the area covered by previous deep-field space UV data combined, reaching a depth of about 27 and 28 ABmag (5σ in 0.”2 apertures) for F275W and F435W, respectively. Along with new photometric catalogs, we present an analysis of the rest-frame UV luminosity function (LF), relying on our UV-optimized aperture photometry method, yielding a factor of 1.5 increase over H-isophot aperture photometry in the signal-to-noise ratios of galaxies in our F275W imaging. Using well-tested photometric redshift measurements, we identify 5810 galaxies at redshifts 0.6 &lt; z &lt; 1, down to an absolute magnitude of M UV = −14.2. In order to minimize the effect of uncertainties in estimating the completeness function, especially at the faint end, we restrict our analysis to sources above 30% completeness, which provides a final sample of 4726 galaxies at −21.5 &lt; M UV &lt; −15.5. We performed a maximum likelihood estimate to derive the best-fit parameters of the UV LF. We report a best-fit faint-end slope of α=−1.359−0.041+0.041 at z ∼ 0.8. Creating subsamples at z ∼ 0.7 and z ∼ 0.9, we observe a possible evolution of α with redshift. The unobscured UV luminosity density at M UV &lt; −10 is derived as ρUV=1.339−0.030+0.027(×1026ergs−1Hz−1Mpc−3) using our best-fit LF parameters. The new F275W and F435 photometric catalogs from UVCANDELS have been made publicly available on the Barbara A. Mikulski Archive for Space Telescopes