Cytokine release syndrome in COVID-19 patients, a new scenario for an old concern. The fragile balance between infections and autoimmunity

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk

A comprehensive picture of baryons in groups and clusters of galaxies

(Abridged) Based on XMM-Newton, Chandra and SDSS data, we investigate the baryon distribution in groups and clusters and its use as a cosmological constraint. For this, we considered a sample of 123 systems, with total masses in the mass range M500 = ~ 10^13 - 4 x 10^15 h_70^-1 Msun. The gas masses and total masses are derived from X-ray data under the assumption of hydrostatic equilibrium and spherical symmetry. The stellar masses are based on SDSS-DR8 data. For the 37 systems out of 123 that had both optical and X-ray data available, we investigated the gas, stellar and total baryon mass fractions inside r2500 and r500, and the differential gas mass fraction within the spherical annulus between r2500 and r500, as a function of total mass. For the other objects, we investigated the gas mass fraction only. We find that the gas mass fraction inside r2500 and r500 depends on the total mass. However, the differential gas mass fraction does not show any dependence on total mass for systems with M500 > 10^14 Msun. We find that the total baryonic content increases with cluster mass. This led us to investigate the contribution of the ICL to the total baryon budget for lower mass systems, but we find that it cannot account for the difference observed. The gas mass fraction dependence on total mass observed for groups and clusters could be due to the difficulty of low-mass systems to retain gas inside the inner region. Due to their shallower potential well, non-thermal processes are more effective in expelling the gas from their central regions outwards. Since the differential gas mass fraction is nearly constant it provides better constraints for cosmology. Using our total f_b estimates, our results imply 0.17 < Omega_m < 0.55.Comment: Accepted for publication in A&A; 16 pages, 9 figures, 1 tabl

Differential diagnosis of endometriosis by ultrasound: A rising challenge

Ultrasound is an effective tool to detect and characterize endometriosis lesions. Variances in endometriosis lesions’ appearance and distorted anatomy secondary to adhesions and fibrosis present as major difficulties during the complete sonographic evaluation of pelvic endometriosis. Currently, differential diagnosis of endometriosis to distinguish it from other diseases represents the hardest challenge and affects subsequent treatment. Several gynecological and non-gynecological conditions can mimic deep-infiltrating endometriosis. For example, abdominopelvic endometriosis may present as atypical lesions by ultrasound. Here, we present an overview of benign and malignant diseases that may resemble endometriosis of the internal genitalia, bowels, bladder, ureter, peritoneum, retroperitoneum, as well as less common locations. An accurate diagnosis of endometriosis has significant clinical impact and is important for appropriate treatment

Beyond Sentinel Lymph Node: Outcomes of Indocyanine Green-Guided Pelvic Lymphadenectomy in Endometrial and Cervical Cancer

Background: The aim of our study was to compare the number of lymph nodes removed during indocyanine green (ICG)-guided laparoscopic/robotic pelvic lymphadenectomy with standard systematic lymphadenectomy in endometrial cancer (EC) and cervical cancer (CC). Methods: This is a multicenter retrospective comparative study (Clinical Trial ID: NCT04246580; updated on 31 January 2023). Women affected by EC and CC who underwent laparoscopic/robotic systematic pelvic lymphadenectomy, with (cases) or without (controls) the use of ICG tracer injection within the uterine cervix, were included in the study. Results: The two groups were homogeneous for age (p = 0.08), Body Mass Index, International Federation of Gynaecology and Obstetrics (FIGO) stages (p = 0.41 for EC; p = 0.17 for CC), median estimated blood loss (p = 0.76), median operative time (p = 0.59), and perioperative complications (p = 0.66). Nevertheless, the number of lymph nodes retrieved during surgery was significantly higher (p = 0.005) in the ICG group (n = 18) compared with controls (n = 16). Conclusions: The accurate and precise dissection achieved with the use of the ICG-guided procedure was associated with a higher number of lymph nodes removed in the case of systematic pelvic lymphadenectomy for EC and CC

Clinical Prognostic Factors in Patients With Metastatic Adrenocortical Carcinoma Treated With Second Line Gemcitabine Plus Capecitabine Chemotherapy

Gemcitabine plus Capecitabine (Gem/Cape) is a frequently adopted second line chemotherapy for metastatic adrenocortical carcinoma (ACC), but only a minority of patients is destined to obtain a clinical benefit. The identification of baseline predictive factors of efficacy is relevant. We retrospectively analyzed clinical data from 50 consecutive patients with metastatic progressing ACC treated between 2011 and 2019. Patients received intravenous Gemcitabine and oral Capecitabine on a metronomic schedule. Previous mitotane therapy was maintained. Clinical benefit (partial response + stable disease) at 4 months was 30%, median progression-free survival (PFS) and disease-specific survival (DSS) from Gem/Cape start were 3 and 8 months, respectively. Among clinical variables evaluated before the start of Gem/Cape, presence of ECOG performance status ≥1 [HR 6.93 95% confidence interval (CI) 0.03–0.54, p.004] and neutrophil-to-lymphocyte ratio (NLR) ≥5 [HR 3.88, 95% (CI) 0.81–0.90, p.003] were independent indicators of poor PFS at multivariate analysis. Conversely, surgery of primary tumor, the presence of lung or lymph-node metastases, blood mitotane level, anemia, and the Advanced Lung cancer Inflammation index (ALI) failed to be independently associated. This study confirms that the Gem/Cape schedule is modestly active in heavily pretreated ACC patients (28% received at least two previous chemotherapy lines). NLR and performance status (PS) are easily available clinical parameters that are helpful to identify patients not likely to derive significant advantage from Gem/Cape chemotherapy

A Multicenter Retrospective Cohort Study Evaluating the Clinical Outcomes of Patients with Coagulopathy Undergoing Transcatheter Arterial Embolization (TAE) for Acute Non-Neurovascular Bleeding

Background and Objectives: Transcatheter arterial embolization (TAE) is the mainstay of treatment for acute major hemorrhage, even in patients with coagulopathy and spontaneous bleeding. Coagulopathy is associated with worsening bleeding severity and higher mortality and clinical failure rates. Furthermore, some unanswered questions remain, such as the definition of coagulopathy, the indication for TAE or conservative treatment, and the choice of embolic agent. This study aims to assess the efficacy and safety of TAE for spontaneous non-neurovascular acute bleeding in patients with coagulopathy. Materials and Methods: This study is a multicenter analysis of retrospectively collected data of consecutive patients with coagulopathy who had undergone, from January 2018 to May 2023, transcatheter arterial embolization for the management of spontaneous hemorrhages. Results: During the study interval (January 2018–May 2023), 120 patients with coagulopathy underwent TAE for spontaneous non-neurovascular acute bleeding. The abdominal wall was the most common bleeding site (72.5%). The most commonly used embolic agent was polyvinyl alcohol (PVA) particles or microspheres (25.0%), whereas coils and gelatin sponge together accounted for 32.5% of the embolic agents used. Technical success was achieved in all cases, with a 92.5% clinical success rate related to 9 cases of rebleeding. Complications were recorded in 12 (10%) patients. Clinical success was significantly better in the group of patients who underwent correction of the coagulopathy within 24 h of TAE. Conclusions: Transcatheter arterial embolization (TAE) is effective and safe for the management of acute non-neurovascular bleeding in patients with coagulopathy. Correction of coagulopathy should not delay TAE and vice versa, as better clinical outcomes were noted in the subgroup of patients undergoing correction of coagulopathy within 24 h of TAE

Using INTERCheck® to Evaluate the Incidence of Adverse Events and Drug–Drug Interactions in Out- and Inpatients Exposed to Polypharmacy

Background: Polypharmacy exposes patients with comorbidities (particularly elderly patients) to an increased risk of drug-specific adverse events and drug–drug interactions. These adverse events could be avoided with the use of a computerized prescription support system in the primary care setting. The INTERCheck® software is a prescription support system developed with the aim of balancing the risks and benefits of polytherapy and examining drug–drug interactions. Objectives: This observational study used the INTERCheck® software to evaluate the incidence of adverse events and of drug–drug interactions in outpatients and inpatients receiving multiple medications. Methods: Patients were randomly enrolled from the outpatient department (n = 98) and internal medicine ward (n = 46) of S. Andrea Hospital of Rome. Polypharmacological treatment was analyzed using INTERCheck® software, and the prevalence of risk indicators and adverse events was compared between the two groups. Results: Polypharmacy (use of five or more drugs) applied to all except three cases among outpatients and one case among inpatients. A significant positive correlation was found between the number of medications and the INTERCheck® score (ρ = 0.67; p &lt; 0.000001), and a significant negative correlation was found between the drug-related anticholinergic burden and cognitive impairment (r = −&nbsp;0.30 p = 0.01). Based on the INTERCheck® analysis, inpatients had a higher score for class D (contraindicated drug combination should be avoided) than did outpatients (p = 0.01). The potential class D drug–drug interactions were associated with adverse events that caused hospitalization (χ2 = 7.428, p = 0.01). Conclusions: INTERCheck® analysis indicated that inpatients had a high risk of drug–drug interactions and a high percentage of related adverse drug events. Further prospective studies are necessary to evaluate whether the INTERCheck® software may help reduce polypharmacy-related adverse events when used in a primary care setting and thus potentially avoid related hospitalization and severe complications such as physical and cognitive decline

Transcatheter arterial embolization (TAE) of cancer-related bleeding

Background and Objectives: Roughly 10% of cancer patients experience an episode of bleeding. The bleeding severity can range from occasional trivial bleeds to major bleeding. The treatment for the bleeding may vary, depending on the clinical condition and anatomical site, and may include various strategies, among which TAE is a cornerstone of major bleeding management. However, the existing literature on tumor hemorrhages is inconsistent. The objective of this multicenter retrospective cohort study was to evaluate the effectiveness and safety of arterial embolization in the treatment of tumor hemorrhages in patients with solid cancers. Materials and Methods: The data for patients with solid cancers undergoing TAE for the management of tumor hemorrhages from January 2020 to May 2023 were gathered. Results: A total of 92 patients with cancer-related bleeding were treated between January 2020 and May 2023. No bleeding was detected by X-ray angiography (XA) in 12 (13%) cases; therefore, a blind embolization was performed. The most common bleeding site was the liver (21.7%). A total of 66 tumor hemorrhages were spontaneous. The most commonly used embolic agent was polyvinyl alcohol (PVA) particles (30.4%). Technical success was achieved in 82 (89.1%) cases, with an 84.8% clinical success rate related to 14 cases of rebleeding. Proximal embolization was performed for 19 (20.7%) patients. Complications were recorded for 10 (10.9%) patients. The 30-day bleeding-related mortality was 15.2%. The technical success, clinical success, proximal embolization rate, and 30-day rebleeding were worse in the subset of patients undergoing TAE with coils. Conclusions: Transcatheter arterial embolization (TAE) represents a viable and potentially life-saving therapeutic approach in the management of tumor hemorrhages, demonstrating a notable effectiveness and safety. The TAE of bleeding tumors using coils resulted in a higher rate of non-superselective proximal embolization, with a trend toward lower clinical success rates and higher rebleeding episodes

Extreme AGN Feedback and Cool Core Destruction in the X-ray Luminous Galaxy Cluster MACS J1931.8-2634

We report on a deep, multiwavelength study of the galaxy cluster MACS J1931.8-2634 using Chandra X-ray, Subaru optical, and VLA 1.4 GHz radio data. This cluster (z=0.352) harbors one of the most X-ray luminous cool cores yet discovered, with an equivalent mass cooling rate within the central 50 kpc is approximately 700 solar masses/yr. Unique features observed in the central core of MACSJ1931.8-2634 hint to a wealth of past activity that has greatly disrupted the original cool core. We observe a spiral of relatively cool, dense, X-ray emitting gas connected to the cool core, as well as highly elongated intracluster light (ICL) surrounding the cD galaxy. Extended radio emission is observed surrounding the central AGN, elongated in the east-west direction, spatially coincident with X-ray cavities. The power input required to inflate these `bubbles' is estimated from both the X-ray and radio emission to reside between 4 and 14e45 erg/s, putting it among the most powerful jets ever observed. This combination of a powerful AGN outburst and bulk motion of the cool core have resulted in two X-ray bright ridges to form to the north and south of the central AGN at a distance of approximately 25 kpc. The northern ridge has spectral characteristics typical of cool cores and is consistent with being a remnant of the cool core after it was disrupted by the AGN and bulk motions. It is also the site of H-alpha filaments and young stars. The X-ray spectroscopic cooling rate associated with this ridge is approximately 165 solar masses/yr, which agrees with the estimate of the star formation rate from broad-band optical imaging (170 solar masses/yr). MACS J1931.8-2634 appears to harbor one of most profoundly disrupted low entropy cores observed in a cluster, and offers new insights into the survivability of cool cores in the context of hierarchical structure formation.Comment: 19 pages, 15 figures, 5 tables. Accepted by MNRAS for publication September 30 201