Severe Infectious Complications Research Articles

The DNA-dependent protein kinase catalytic subunit promotes sepsis-induced cardiac dysfunction through disrupting INF-2-dependent mitochondrial dynamics.

Sepsis-induced cardiomyopathy (SIC) represents a severe complication of systemic infection, characterized by significant cardiac dysfunction. This study examines the role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Inverted Formin 2 (INF2) in the pathogenesis of SIC, focusing on their impact on mitochondrial homeostasis and dynamics. Our research demonstrates that silencing DNA-PKcs alleviates lipopolysaccharide (LPS)-induced cardiomyocyte death and dysfunction. Using HL-1 cardiomyocytes treated with LPS, we observed that DNA-PKcs knockdown notably reverses LPS-induced cytotoxicity, indicating a protective role against cellular damage. This effect is further substantiated by the reduction in caspase-3 and caspase-9 activation, key markers of apoptosis, upon DNA-PKcs knockdown. Besides, our data further reveal that DNA-PKcs knockdown attenuates LPS-induced mitochondrial dysfunction, evidenced by improved ATP production, enhanced activities of mitochondrial respiratory complexes, and preserved mitochondrial membrane potential. Moreover, DNA-PKcs deletion counteracts LPS-induced shifts towards mitochondrial fission, indicating its regulatory influence on mitochondrial dynamics. Conclusively, our research elucidates the intricate interplay between DNA-PKcs and INF2 in the modulation of mitochondrial function and dynamics during sepsis-induced cardiomyopathy. These findings offer new insights into the molecular mechanisms underpinning SIC and suggest potential therapeutic targets for mitigating mitochondrial dysfunction in this critical condition.

Experience with the combination of tixagevimab + cilgavimab for pre-exposure prophylaxis of COVID-19 in cancer patients: A retrospective analysis

Background. COVID-19 (COrona VIrus Disease 2019) is a serious threat to cancer patients, who are at an increased risk of severe infection complications. Pre-exposure prophylaxis with a combination of monoclonal antibodies, tixagevimab-cilgavimab (Evusheld), has been shown to be effective in preventing COVID-19, reducing hospital admission rate and mortality in immunocompromised individuals.
 Aim. To describe the experience of using tixagevimab-cilgavimab for pre-exposure prophylaxis of COVID-19 in the Russian population of patients with solid tumors receiving antitumor drug therapies.
 Materials and methods. The retrospective analysis included case histories of 79 patients (57% females and 43% males) with solid tumors treated at the Moscow City Clinical Oncology Hospital No. 1 from October 2022 to June 2023. All patients received tixagevimab-cilgavimab for COVID-19 pre-exposure prophylaxis.
 Results. The mean age was 64±11 years (32 to 83 years). Seventy-three percent of patients received cytotoxic therapy, associated with an increased risk of infectious complications, including COVID-19. No immediate or delayed adverse events related to tixagevimab-cilgavimab were reported. During the observation period since the drug injection, 3 (3.8%) new mild cases of COVID-19 were reported.
 Conclusion. Tixagevimab-cilgavimab (Evusheld) is safe and effective for pre-exposure prophylaxis of COVID-19 in the Russian population of patients with solid tumors receiving antitumor drug therapy.

Rancangan video animasi edukasi kesiapsiagaan bencana non alam COVID-19 bagi ibu hamil. Uji validitas dan reliabilitas instrumen

Background: COVID-19 is transmitted through air transmission. Prevention of transmission of the COVID-19 virus in pregnant women will certainly reduce complications in pregnant women and the fetus. An educational animated video design can help increase pregnant women's understanding of preventing the transmission of COVID-19. The Coronavirus disease 2019 or COVID-19 in pregnant women will increase the risk of severe infection and pregnancy complications such as preterm labour. Pregnancy will cause physiological changes and maternal immunity, so pregnant women are in a high-risk group for COVID-19 infection. Prevention of COVID-19 virus transmission in pregnant women needs to be done to prevent complications in pregnant women and fetuses. Research objectives: The design of educational animated videos can help increase the understanding of pregnant women in preventing COVID-19 transmission and to test the validity and reliability of instruments.Method: Developing an educational video animation for non-natural disaster preparedness is carried out in several stages, namely making scenarios, storyboards, sketches, choosing colors, coloring, layering and combining them into animated videos. Then, the animated video was validated by a team of experts from the Langsa City Health Office. The content of this video is about preventing COVID-19 transmission in pregnant women. The animated video was tested on 20 respondents in June 2021 in Karang Anyar village, Langsa City. Furthermore, the instrument was tested for validity and reliability on 20 respondents in July 2021 in Paya Bujok Tunong Village, Langsa City.Results: Are 10 components assessed from educational animated videos, and the majority are very good ≥65%. The results of the validity and reliability tests show that the questionnaire is suitable for use in the condition of pregnant women when facing COVID-19 (p > 0,05). However, one invalid statement item was found. The reliability test results show that all variables have an alpha value above 0,378.Conclusion: Respondents can use and distribute animated videos and research instruments.

How do we prevent severe intra-abdominal infectious complications following minimally invasive gastrectomy for cancer? The usefulness of a novel marker using computed tomography images (minimum umbilicus-vertebra diameter) and robotic surgery.

Intra-abdominal infectious complications (IAICs) following minimally invasive gastrectomy (MIG) for cancer sometimes worsen short- and long-term outcomes. In this study, we focused on the minimum umbilicus-vertebra diameter (MUVD) in preoperative computed tomography (CT) images and robotic surgery to prevent severe IAIC occurrence. A total of 400 patients with gastric cancer who underwent 204 laparoscopic gastrectomy (LG) and 196 robotic gastrectomy (RG) procedures were enrolled in this study. We retrospectively investigated the significance of the MUVD and robotic surgery for preventing severe IAICs following MIG using multivariate and propensity score matching analysis. The MUVD cutoff value was 84 mm by receiver operating characteristic (ROC) curve using severe IAICs as the end point. The MUVD and visceral fat area (VFA) had significantly higher area under the curve (AUC) than BMI (MUVD vs. BMI, p = 0.032; VFA vs. BMI, p < 0.01). In the multivariate analysis, high MUVD (HR, 9.46; p = 0.026) and laparoscopic surgery (HR, 3.35; p = 0.042) were independent risk factors for severe IAIC occurrence. In the propensity matching analysis between robotic and laparoscopic surgery in the high MUVD group, the RG group tended to have a lower severe IAIC rate than the LG group (0% vs. 9.8%, p = 0.056). The MUVD was a novel and easy-measuring predictor of severe IAICs following MIG. Robotic surgery should be considered first in patients with gastric cancer having an MUVD value of 84 mm or higher from the perspective of severe IAIC occurrence.

The Efficacy and Safety of the Third Generation TKI Olverembatinib in Adult Ph+ Acute Lymphoblastic Leukemia with Relapsed Disease or Persistent MRD Bridging to Allo-HSCT: A Case Series from a Single Center

Background The value of achieving hematology remission and MRD negativity before HSCT is substantial for ph+ALL patients. Olverembatinib, a novel third-generation TKI developed in China, has been approved in CML with T315I mutation since 2021. In this study, we report a retrospective analysis of the efficacy and safety of the Olverembatinib-involved regimen in adult Ph/BCR-ABL1+ ALL with relapsed disease or persistent MRD prior to allo-HSCT. Herein, we report our preliminary results. Method In this retrospective analysis, all enrolled ph+ALL patients with relapsed disease or persistent MRD were treated with Olverembatinib involving regimen, before bridging to HSCT. The Olverembatinib involving regimen included: Olverembatinib and Venetoclax in combination with VP based low intensive chemotherapy (Vindesine /Prednisone), Olverembatinib+Blinatumomab, Olverembatinib + INO. Efficacy was assessed by complete remission (CR) rate, MRDneg (&amp;lt;0.01%) rate by flow cytometry, and CMR (BCR-ABL1 transcript&amp;lt;10-4) rate by real-time quantitative polymerase chain reaction (RT-qPCR). Safety events were also monitored. Result From April 2022 to February 2023, 13 Ph+ ALL pts were treated with Olverembatinib involving therapy due to disease recurrence (n=2) and persistently molecular positive (n=11). The median age was 40 years (range, 23-56), and 9/13 were males. BCR::ABL1 p190 and p210 fusion were found in 7 and 6 patients, respectively. Three patients had T315I mutations, and one had G250E mutation. Three patients had IKZF mutations. Four patients had received 2 types of TKIs previously. One patient relapsed with both BM and CNS involved. The median time from diagnosis of Relapse or molecular positive to the administration of Olverembatinib was 181 (range, 51-1284) days. Totally, ten patients achieved CMR, and the overall CMR by PCR rate was 76.92%, while the MRDneg rate by flow cytometry was 100%. All patients with T315I mutations achieved CMR. Among patients with hematology relapse, the hematology remission rate and CMR rate reached both 100% after only one cycle of Olverembatinib involved regimen, including Olverembatinib + Blinatumomab, Olverembatinib + INO, respectively. For patients with persistent molecular diseases, eight patients achieved CMR. With respect to the different olverembatinib involving regimen, the CMR in olverembatinib+Venetoclax+ VP, olverembatinib+Blinatumomab, olverembatinib + INO, were 71.43%. 75% and 100%, respectively. The median regimen cycle times were 2 (range 1-3). All patients succeeded to bridge to allo-HSCT. With a median follow-up of 249（60-376）days post-HSCT, the estimated one-year overall survival (OS), and relapse-free survival (RFS) were 92.3±7.39% and 92.3±7.39%, respectively. One patient died of severe infection and CNS complications. Meanwhile, the Olverembatinib-based therapy was well tolerated. Only one patient reported gastrointestinal symptoms, such as nausea and vomiting. One patient complained about dizziness due to hypertension. No drug-related death or permanent discontinuation was reported due to toxicity. Conclusion This work suggests that Olverembatinib showed a profound response rate and was well tolerated in MRD clearance prior to allo-HSCT in Ph+ALL with disease recurrence and persistently MRD positive. Larger prospective studies are needed.

Treosulfan Based Haploidentical Αß T Cell Depleted HSCT Represents a Curative Alternative in Pediatric and Adult Patients with Transfusion Dependent Thalassaemia

Background: Quality of life remains severely compromised in patients suffering from Transfusion Dependent Thalassemia (TDT) despite optimal supportive care. HSCT with a MSD, the current curative option, achieving a 92.1% 2y-OS in children and 84.4% in adults (EBMT registry). Unfortunately, availability of MDs is limited, so that haploidentical HSCT is increasingly explored. Methods: 13 TDT patients (median age: 11 years; range: 2-23) received either a CD3 +/CD19 + (n=4; all class II/III) or αß/CD19 + (n=10; 7 class II, II/III) T-haplo-HSCT and were compared with 8 TDT-patients (7 class II, II/III, III) receiving a BM graft from a MSD (median age: 11 years; range: 4-22). Indication for T-haplo HSCT patients was severe iron overload/ transfusion-associated complications. All patients received an identical conditioning regimen consisting of treosulfan, thiotepa, fludarabine (FTT) and ATG-Grafalon, with the only difference in the timing of ATG (upfront in T-haplo-HSCT, prior to d0 in MSD-HSCT). Immunosuppression (IST) was maintained for a minimum of 180 days consisting of calcineurin inhibitors (mainly tacrolimus) and MMF. Results: The OS and DFS for MSD and T-haplo-HSCT was 100%/100% and 100%/92%, respectively (Table 1). The median follow-up was 30 months for MSD (range 4-72) and 38 months for T-haplo-HSCT (range 4-86). Neutrophil engraftment was achieved after a median of 31 days for MSD patients and 17 days for T-haplo-HSCT with a median of 5 x 10 8 TNC/kg (range: 3.28-7.88) and 15 x 10 6 CD3 +/CD19 + or αβ/CD19 + depleted CD34 + cells/kg (range: 9.2-24.2), respectively. One patient received two T-haplo HSCT, due to primary graft failure partly due to a major AB0 incompatibility. A mixed chimerism was observed in 3/7 MSD-HSCT (median 92%; range 27.5-100%) and in T-haplo-HSCT in 2/13 patients (median 99%; range: 45.3 -100%). Transfusion independence was achieved in all MSD and in all but one T-haplo patient. In MSD and in T-haplo-HSCT, IST was terminated after a median of 173 days and 226 days (range: 112-347), respectively. MSD patients reached CD4 counts &amp;gt;50/µl on day +43 (median; range: 25-125) and T-haplo-HSCT patients on day +114 (median; range: 33-173). The treosulfan-based conditioning regimen was well tolerated with no VOD/SOS observed in this high-risk population. No case of acute or chronic Graft-versus-Host disease (GvHD) was observed in the MSD population. In T-haplo-HSCT, 3 patients experienced grade I acute GvHD (skin) which resolved with prednisolone and in 2 cases with additional extracorporeal photopheresis. Only the oldest patient experienced mild chronic skin GvHD, which resolved by day +580. No severe infectious complications occurred despite a prolonged chimerism-triggered weaning of the IST. Conclusions: Independent of donor availability, graft rejection and iron-overload related organ damage (VOD/SOS) are major pitfalls in transplanting advanced stage TDT patients. Treosulfan demonstrated to be an excellent alternative to busulfan in this setting reflected in the safety and efficacy data of this pilot series. Overall, outcomes of T-haplo-HSCT in TDT are very encouraging with a competitive OS, so that a transplant indication in pediatric and AYA TDT patients lacking a MD is feasible.

Comprehensive Geriatric Assessment in Diffuse Large B-Cell Lymphomas Patients Older Than 70 Years Old: Prospective Single-Center Experience

CONCLUSIONS Diffuse large B-cell lymphoma (DLBCL) is diagnosed at a median age of 65 years, and around 40% of the patients are older than 70 years. Because of frailty and comorbidities, standard chemoimmunotherapy delivery may be very challenging in this setting. Therefore, a more personalized approach based on comprehensive geriatric assessment (CGA) may be warranted, as already proposed by other international groups. We aim to evaluate the impact of the establishment of a CGA on therapeutic decisions and outcome in our older population of pts with DLBCL. From January 2018 to May 2023, some unselected (depending on the referring hematologist) patients ≥70 years old with DLBCL were prospectively evaluated by a geriatrician at Catalan Institute of Oncology. CGA included validated instruments to assess: comorbidity with Charlson Index and Cumulative Illness Rating Scale (CIRS); polypharmacy; functional status in terms of activities daily living (ADL) with Barthel scale and instrumental ADL with Lawton scale; geriatric syndromes; mood with Yeasauvage scale; cognition with Pfeiffer scale; and social status. According to global CGA, patients were classified in 3 frailty groups: type 1, fit for standard chemoimmunotherapy (S-CT); type 2, fit for reduced intensity chemoimmunotherapy (RI-CT); type 3, candidate to palliative treatment. Among 247 newly diagnosed DLBCL, 101 (41%) patients had ≥70 years, of which 38 underwent CGA. Among patients who underwent CGA, 14 (37%) were classified as type 1, 20 (53%) type 2 and 4 (10%) type 3. Type 1 patients were younger (median age 75, ≥80 yrs 29%), than type 2 (median age 79, ≥80 yrs 55%), and type 3 (median age 93, ≥80 yrs 100%). The characteristics of 63 pts ≥70 years who did not underwent CGA did not differ significantly from the population in the study, except they had lower extranodal involvement and a higher proportion of patients did not received treatment (Table 1). All the evaluated 38 patients received treatment (Figure 1), 34 with immunochemotherapy (Table 1), and 5 patients (4 of type 3 and 1 of type 2) were palliatively handled: 1 with radiotherapy and 4 with cyclophosphamide monotherapy with or without prednisone. During treatment, 2 patients (one of type 1 and one of type 2) were deescalated from RCHOP to RminiCHOP due to severe infectious complications, while 6 patients of type 2 were upgraded, as previously planned if treatment was well tolerated. The most common adverse event was infection in 36% of patients (in 21% grade 3/4). Twelve patients (4 of type 1 and 8 of type 2) experienced at least an infectious event. Two toxic fatal events (1 patient of type 2 of septic shock and 1 of type 1 of urinary tract infections in the contest of bladder fistula) were reported. There were treatment delays in 10 (29%) patients (5 of type 1 and 5 of type 2). Among 33 patients who received active treatment, 4 had not been evaluated yet, and 29 were evaluable for response: overall response rate (ORR) was 71% and the complete remission (CR) rate was 68% (71% with S-CT and 68% with RI-CT). With a median follow-up of 12 months (range, 1-133), the 1-year event-free survival (EFS) and overall survival (OS) of the study population were 57% (95% CI, 38-71) and 72% (95% CI, 52-84), respectively. Among patients without CGA, the 1-year EFS and OS were 57% (95% CI, 44-69) and 67% (95% CI, 53-78), respectively. According to CGA, the 1-year EFS of type 1 patients was 68% (95% CI 35-87), type 2 was 61% (95% CI, 34-79) and type 3 was 0%. The 1-year OS of type 1 patients was 66% (95% CI 32-86), type 2 was 82% (95% CI, 52-94) and type 3 was 50% (95% CI, 1-84) (Figure 1). In this homogeneous series of older patients with DLBCL, our results confirmed the importance of CGA. Within a multidisciplinary approach, we may accurately classify the fitness of patients and offer them the best therapeutic options without causing excessive toxicity, as proved by similar EFS estimates between type 1 and 2 subgroups. Further larger studies are needed to evaluate potential geriatric interventions aimed at further improving outcomes.

THROMBOTIC AND THROMBOEMBOLIC COMPLICATIONS OF A NEW CORONAVIRUS INFECTION COVID-19 A MEDICAL WORKER (A CLINICAL CASE WITH AN UNFAVORABLE OUTCOME)

The presented clinical case describes severe complications of a new coronavirus infection (COVID-19) in a comorbid patient with obliterating atherosclerosis of the arteries of the lower extremities, varicose veins of the lower extremities, hypertension, in the form of late thrombosis of the arteries of the lower extremities with the development of gangrene, which was the basis for amputation of the limb. The development, in the future, of complications such as: thromboembolism of the branches of the pulmonary artery and acute left ventricular failure, which caused a fatal outcome. The principles and results of the medical examination conducted in order to establish a causal relationship of the disease with the professional activity of a medical worker are presented. The need for a multidisciplinary approach to the early diagnosis, prevention and treatment of COVID-19 and its complications, improving the mechanisms of admission to the professional activities of medical workers taking into account age and comorbid conditions in conditions of high risk of infection with SARS-CoV-2 is emphasized.

Applying the Novel EHA/EBMT Grading System for Icaht Following CAR-T Therapy: Comparative Incidence across Disease Entities and Association with Infections and Mortality

Background: Hematological toxicity is a frequent side effect of CAR-T therapy and predisposes for severe infectious complications. Recently, the EHA/EBMT consensus grading for Immune Effector Cell Associated HematoToxicity (ICAHT) was developed ( Rejeski et al. Blood 2023). In contrast to existing grading systems such as the CTCAE, the novel ICAHT grading integrates both the depth and duration of neutropenia. We hypothesized that ICAHT severity is associated with key clinical sequelae such as transfusion requirements, hospitalization, severe infections, and adverse treatment outcomes. Methods: We applied the novel grading of early ICAHT (day 0-30) to a multicenter retrospective real-world cohort of 549 patients treated with BCMA- or CD19-directed CAR T-cells for relapsed/refractory B-cell malignancies (334 large B-cell lymphoma [LBCL], 112 multiple myeloma [MM], 103 mantle cell lymphoma [MCL]) across twelve international sites (Germany, France, Spain, USA). Hematotoxicity endpoints included the total cumulative duration of severe neutropenia (ANC &amp;lt;500/µL, day 0-60) and phenotypes of neutrophil recovery ( Rejeski et al. Blood 2021). Infections were studied until day +90 after CAR-T and were graded on a 5-grade scale as mild, moderate, severe, life-threatening, or fatal. Non-relapse mortality (NRM) was defined as death following CAR-T without evidence of relapse or progression. Kaplan-Meier estimates of progression-free (PFS) and overall survival (OS) were compared using log-rank test. Results: Our study cohort included 424 patients without severe ICAHT (absent or grade 1-2) and 125 patients with severe ICAHT (grade 3-4). The distribution of mild (1°), moderate (2°), severe (3°) and life-threatening (4°) ICAHT was 36%, 29%, 17%, and 5%. Seventy patients (13%) did not develop ICAHT of any grade. When comparing ICAHT grades across disease entities, we noted a numeric trend towards increased severe ICAHT in MCL compared to LBCL or MM patients (Grade ≥3: 28% vs. 23% vs. 15%). Patients that subsequently developed severe ICAHT displayed elevated serum inflammatory markers and pronounced cytopenia at baseline - reflected by increased CAR-HEMATOTOX scores (median 3 vs. 1, p&amp;lt;0.0001). On multivariate binary logistic regression, co-stimulatory domain (CD28z), low platelet count, low ANC, low hemoglobin, increased serum ferritin, and the presence of bone marrow infiltration were independent risk factors for severe ICAHT. We noted a strong positive correlation between ICAHT severity and the cumulative duration of severe neutropenia (r=0.92, p&amp;lt;0.0001). The aplastic phenotype of neutrophil recovery was enriched in patients with grade 3 (73%) and especially grade 4 ICAHT (100%). Severe ICAHT was also associated with coincident multilineage cytopenias, resulting in increased transfusion requirements for both platelets (85% vs. 21%, p&amp;lt;0.0001) and red blood cells (86% vs. 41%, p&amp;lt;0.0001). In terms of management of hematotoxicity, the severe ICAHT group more commonly received G-CSF (72% vs. 44%, p=0.01), TPO mimetics (12% vs. 2%, p&amp;lt;0.0001) and hematopoietic stem cell boosts (6% vs. 0.2%, p&amp;lt;0.0001). Importantly, patients with severe ICAHT displayed a significantly increased rate of severe infections (49% vs. 13%, p&amp;lt;0.0001, Fig. 1a) and severe bacterial infections (36% vs. 8%, p&amp;lt;0.0001). This translated into a markedly increased 1-year NRM rate (14% vs. 4.5%, logrank p&amp;lt;0.0001, Fig. 1b), which was primarily attributed to fatal infections of fungal or bacterial origin. Of note, the ICAHT grading showed superior discrimination for severe infections (C-index 0.73, 95%CI: 0.67-0.78) compared to CTCAE grading (C-index 0.55, n.s.). Prolonged hospitalization was noted in case of severe ICAHT (median 21 vs. 16 days, p&amp;lt;0.0001) and intensive care admission was more common (23% vs. 4%, p&amp;lt;0.001). Finally, we observed inferior PFS (1-year PFS 35% vs. 51%, median 4 vs. 14 months, p&amp;lt;0.0001) and inferior OS (1-year OS 52% vs. 73%, median 12 months vs. not-reached, p&amp;lt;0.0001) in the patients that developed severe ICAHT. Conclusions: These data highlight the clinical relevance of the novel EHA/EBMT ICAHT grading system. Importantly, ICAHT severity was closely associated with transfusion dependence, increased infection incidence, and adverse treatment outcomes with high NRM. Taken together, these findings argue for reporting ICAHT grades in clinical trials evaluating established and novel CAR constructs.

Abstract 077: Readmission Rates and Etiologies among Patients with Subarachnoid Hemorrhage: A Nationwide United States Analysis

Introduction Subarachnoid Hemorrhage (SAH) is the leading cause of morbidity and mortality in stroke patients, associated with severe neurological, infectious, and thromboembolic complications. Identifying clinical predictors linked to hospital readmissions after a SAH allows for the determination of patients with higher risks of complications, opening an avenue for prevention and improved quality of care. Methods The Nationwide Readmission Database (NRD) was used to extract patients with SAH (ICD‐10 code: I60.x) from 2016‐2019. The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 30 and 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results We identified 68,726 patients with SAH, with a mean age of 60.47 years, and 57.86% being female. Overall, 7.79% (n=5354) were readmitted within 30 days and 12.04% (n=8525) were readmitted within 90 days. The rate of 30‐day readmission was overall stable (7.34% in 2016 and 7.70% in 2019; p=0.42), but the 90‐day readmission rate slightly increased from 11.69% in 2016 to 12.47% in 2019 (p=0.04). Around 62% of 90‐day readmissions occurred within the first 30 days. Patients readmitted within 30 days were more likely to be older (mean age = 61.92 vs 60.99 years; p&lt;0.001) and male (43.96% vs 41.74%; p=0.002) compared to those not requiring readmission. They had a higher prevalence of diabetes (23.38% vs 18.82%), hypertension (74.34% vs 70.12%), obesity (13.95% vs 12.25%), dyslipidemia (38.17% vs 33.02%), smoking (39.30% vs 37.43%), prior TIA/ischemic stroke (22.60% vs 20.39%), coronary artery disease (15.03%), DVT (6.06% vs 3.51%), peripheral vascular disease (14.24% vs 11.09%), chronic renal failure (13.34% vs 9.35%), and heart failure (10.57% vs 7.75%) (p&lt;0.001 for all). The most common etiologies of 30‐ and 90‐day readmission were cardiovascular (42.53% and 40.79%), neurological (12.34% and 11.50%), and infectious (8.41% and 8.21%). Conclusion The annual rate of 90‐day readmission, but not 30‐day readmission, increased from 2016 to 2019. Readmitted patients both within 30 and 90 days were more likely to have a higher prevalence of vascular risk factors and related comorbidities.. The most common cause of 30‐ and 90‐day readmission is cardiovascular diseases followed by neurological and infectious conditions. Further studies are required to offer risk stratification and prevention strategies for readmission among patients with Subarachnoid Hemorrhage.

Complications During Root Canal Shaping: A Survey Among Dentists in Morocco

Introduction: Endodontic therapy is a complex procedure that requires a high level of precision due to the intricacies of the root canal system. Despite advancements in endodontic tools and techniques, incidents such as instrument fractures, dentinal plugs, false routes, and root perforations can occur when best practice recommendations are not adhered to. These complications pose a significant public health concern as they can lead to potentially severe infectious complications and ultimately result in endodontic treatment failure. The aim of this study is to elucidate the causes of endodontic complications, particularly during the root canal shaping stage, and to identify strategies for their prevention.Materials and Methods: A cross-sectional, analytical, descriptive, and unidirectional study was conducted on a randomly selected sample of 300 private dentists in Casablanca. The questionnaires were completed anonymously, and statistical analyses were performed using SPSS software. The discussion will be enriched through a comprehensive literature search of major databases, complemented by a series of clinical cases illustrating these complications and the means by which they can be mitigated.Results: The study reveals that 91% of dentists encountered complications during endodontic therapy, with 284 dentists (94.98%) experiencing complications during root canal shaping. The most prevalent complication was instrument fracture, reported by 235 dentists (82.75%). Key contributing factors to these complications included forced file passage, non-adherence to the instrumental sequence, and absence or inadequacy of irrigation. However, these incidents can be averted by adhering to a meticulous treatment protocol and respecting the various steps critical to the success of root canal shaping.Conclusion: In conclusion, there exists a disparity between recommended best practices and the current practices in the field of endodontics, which can lead to multiple complications and subsequent endodontic treatment failures.

Human ApoE2 protects mice against Plasmodium berghei ANKA experimental cerebral malaria.

Cerebral malaria (CM) is the deadliest complication of malaria infection with an estimated 15%-25% mortality. Even with timely and effective treatment with antimalarial drugs such as quinine and artemisinin derivatives, survivors of CM may suffer long-term cognitive and neurological impairment. Here, we show that human apolipoprotein E variant 2 (hApoE2) protects mice from experimental CM (ECM) via suppression of CD8+ T cell activation and infiltration to the brain, enhanced cholesterol metabolism, and increased IFN-γ production, leading to reduced endothelial cell apoptosis, BBB disruption, and ECM symptoms. Our results suggest that hApoE can be an important factor for risk assessment and treatment of CM in humans.

Impact of a robotic system on intra-abdominal infectious complications after minimally invasive gastrectomy in patients with gastric cancer: A propensity score matching analysis regarding visceral obesity.

The efficacy of robotic gastrectomy (RG) on postoperative complications in patients with gastric cancer (GC) is unclear in terms of the volume of intra-abdominal fat tissue. We enrolled 403 patients with GC who had minimally invasive surgery between January 2015 and July 2022. During this time, 197 RG and 206 laparoscopic gastrectomies (LG) were performed on the study participants. According to the computed tomography scan, patients were defined as having or not having visceral obesity based on the visceral fatty area (VFA). In each high and low VFA group, we compared short-term outcomes between the RG group and LG group. After PS matching for patients with high VFA, the two groups were well matched, with 71 cases in both the RG and LG groups. The median surgical time in the RG group was significantly longer (420 vs. 365 min, p < 0.001). However, the RG group had a significantly lower rate of severe intra-abdominal infectious complications (IAIC), such as anastomotic leakage, pancreatic fistula, and intra-abdominal abscess (1.4% vs. 15.4%, p = 0.004). However, among the 77 patients with low VFA values, we found no significant difference in the rate of severe IAIC between the two groups (1.1% in the RG group vs. 2.6% in the LG group, p = 1.00). RG may be a viable alternative to LG because of the lower postoperative IAIC for patients with visceral obesity and GC. However, RG may not benefit non-obese patients.

Is triggering receptor expressed on myeloid cell 1 (TREM-1) protein a new marker of serious infectious complications in colorectal surgery?: case-matched pilot study

PurposeThe purpose of the study was to evaluate the usefulness of the triggering receptor expressed on myeloid cell 1 (TREM-1) protein as a marker for serious infectious complications during laparoscopic colorectal surgery.MethodsSixty-four patients with colon or rectal cancer, who underwent an elective laparoscopic colorectal cancer surgery from November 2018 to February 2020, were included in the analysis. Blood samples of the TREM-1 protein testing were collected four times from each patient: before and on three following postoperative days (PODs). Patients were divided into two groups according to the presence of infectious complications. Subsequently, patients with infectious complications (group 1) were matched 1:1 with patients without complications (group 2). The case-matched analysis was done by selecting patients from the control group by age, ASA scale, cancer stage, and type of surgery.ResultsThere was no significant difference in demographic and operative characteristics between the two groups. The median length of hospital stay was longer in group 1 than in group 2 (11 days vs. 5 days, p < 0.001). Preoperative measurements of TREM-1 protein did not differ between the two groups. There were no significant differences in the measurements on the first and third postoperative days. However, the median TREM-1 measurement was higher in group 1 on the second postoperative day (542 pg/ml vs. 399 pg/ml; p = 0.040). The difference was more apparent when only severe postoperative complications were considered. When compared to the group without any complications, the median TREM-1 level was significantly higher in the group with severe infection complications in POD 1, POD 2, and POD 3 (p < 0.05). The receiver operating characteristic (ROC) curve demonstrated that TREM-1 readings in POD 2 had a sensitivity of 83% and a specificity of 84% for the presence of severe infection complications at a value of 579.3 pg/ml (AUC 0.8, 95%CI 0.65–0.96).ConclusionTREM-1 measurements might become a helpful predictive marker in the early diagnosis of serious infectious complications in patients following laparoscopic colorectal surgery.

The nature of kidney damage causing the development of acute renal failure in patients with COVID-19 (according to morphological studies)

The literature review presents data on the study of the nature of kidney damage in patients with COVID-19 with acute renal insufficiency according to histo-morphological lifetime and postmortem studies of the kidneys during the peak of the epidemic of infection in 2020-2022. In the analysis, the role of direct viral damage to tissues and organ cells is questioned. The frequency of diagnosis of glomerular, tubular, interstitial and vascular lesions is specified, the significance of the presence of variants of the apolipoprotein-1 (APOL1) gene in patients with severe respiratory complications of acute viral infection is assessed.

Immunoadsorption-Based HLA Desensitization in Patients Awaiting Deceased Donor Kidney Transplantation: An Interventional, Non-Randomised, Single Cohort Study.

Whether immunoadsorption (IADS) as part of desensitization protocols could facilitate deceased donor kidney transplantation (KT) in highly sensitized (HS) patients remains to be proven. We retrospectively analyzed our IADS based desensitization protocol for deceased donor KTs between 2013 and 2018. Fifteen HS patients (age 52years [40-56]) were included. Waiting time before IADS was 6years [5-10] and the interval between IADS initiation and KT was 5months [1-12] for the 14 transplanted patients. Nine patients had prior KT. Calculated panel reactive antibody decreased significantly during the protocol (99.3% [92.5-99.9] vs. 79.4% [56.7-81.9]; p = 0.004). Death-censored graft survival was 85.7% at 1 and 2years post-transplantation. One-year median plasma creatinine level was 135µmol/L [111-202]. Six developed active antibody mediated rejection (ABMR) at 1year, with a median delay of 13days [11-26]. Eight patients developed severe infections, including two fatal outcomes. Finally, compared to 93% of patients who received desensitization receiving a KT, only 43% of a control with similar characteristics underwent transplantation. However, no difference was found in overall probability of being alive with a functioning graft at the end of follow-up. The results indicate that our IADS-based desensitization strategy was not effective due to a high rate of ABMR and severe infectious complications which pose a challenge to its universalization.

COVID-19 Associated Myocarditis: Prevalence, Pathophysiology, Diagnosis, and Management.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a pandemic and affected public health greatly. While COVID-19 primarily damages the lungs, leading to cough, sore throat, pneumonia, or acute respiratory distress syndrome, it also infects other organs and tissues, including the cardiovascular system. In particular, myocarditis is a well-recognized severe complication of COVID-19 infection and could result in adverse outcomes. Angiotensin-Converting Enzyme2 is thought to play a pivotal role in SARS-CoV-2 infection, and immune overresponse causes overwhelming damage to the host's myocardium. Direct viral infection and injury do take a part as well, but more evidence is needed to strengthen this proposal. The clinical abnormalities include elevated cardiac biomarkers and electrocardiogram changes and impaired cardiac function that might be presented in echocardiography and cardiovascular magnetic resonance imaging. If necessary, the endomyocardial biopsy would give more forceful information to diagnosis and aid in treatment. Comparisons between COVID-19 myocarditis and other viral myocarditis are also discussed briefly.

Outcomes of COVID-19 in immunocompromised patients: a single center experience.

Malignancy, bone marrow and organ transplantation are associated with deficient and defective immune systems. Immunocompromised patients are at risk for severe and chronic complication of COVID-19 infection. However, the pathogenesis, diagnosis and management of this comorbidity remain to be elucidated. The purpose of the present study was to describe key aspects of COVID-19 infection in immunocompromised patients. In this retrospective, cross-sectional study, lab findings and outcomes of 418 COVID-19 patients with secondary immunodeficiency disorders admitted to Taleghani Hospital in Tehran, from March 2020 to September 2022 were investigated.Of the 418 immunocompromised patients with COVID-19, 236 (56.5%) ‌ were male and the median age of all studied patients was 56.6 ± 16.4 with range of 14 to 92 years. Totally, 198 (47.4%) of the patients died during hospitalization. Remdesivir was used for treatment of all patients. Mortality rate among patients admitted to ICU ward (86.8%) was significantly higher than non ICU admission (p < 0.001). The death rate in patients with CKD was substantially higher than other underlying disease (p < 0.001). In terms of laboratory finding, there was a significant relationship between ICU admission and worse outcome with WBC count (HR = 1.94, 95% CI = 1. 46-2.59, p < 0.001), PMN count (HR = 1.93, 95% CI = 1.452.56, p < 0.001), Hb (HR = 1.49, 95% CI = 1.042.13, p = 0.028), AST (HR = 2.55, 95% CI = 1.913.41, p < 0.001), BUN (HR = 2.56, 95% CI = 2.063.69, p < 0.001), Cr (HR = 2.63, 95% CI = 1.89-3.64, p < 0.001), Comorbidities index (HR = 1.71, 95% CI = 1.29-2.27, p < 0.001) and aging (HR = 1.91, 95% CI = 1.4-2.54, p < 0.001).Immunocompromised status increased the risk of mortality or worse outcome in patients diagnosed with COVID-19. Our finding showed outcome predicting markers in whom the waned immune system encounter new emerging disease and improved our understanding of COVID-19 virus behavior in immunocompromised individuals.

Sinusitis-Induced Orbital Apex Syndrome with Unusual Presentation of Facial Nerve Palsy In HIV-Positive Patient

ABSTRACT Orbital Apex Syndrome (OAS) is a rare ophthalmological disorder characterized by complex symptoms originating from lesions at the orbital apex. Herein, we report a 60-year-old man with a history of diabetes mellitus and hypertension presented with a swollen left eye and sudden visual loss. He also had nasal symptoms before his admission. Treatment includes broad-spectrum antibiotics and antifungals with additional diabetes management and HIV evaluation. OAS, a severe and uncommon complication of a sinusitis infection, can present with diverse symptoms and cause nerve damage in the orbital apical area. The disease can be easily missed or overlooked when it exhibits atypical symptoms in its initial stages. It is crucial to be vigilant and consider the possibility of complications related to the orbital apex for early detection and appropriate treatment. Keywords: Facial Nerve Palsy, HIV, Orbital Apex Syndrome, Sinusitis

The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma

BackgroundBCMA-directed CAR T-cell therapy (CAR-T) has altered the treatment landscape of relapsed/refractory (r/r) multiple myeloma, but is hampered by unique side effects that can lengthen hospital stays and increase morbidity. Hematological toxicity (e.g. profound and prolonged cytopenias) represents the most common grade ≥ 3 toxicity and can predispose for severe infectious complications. Here, we examined the utility of the CAR-HEMATOTOX (HT) score to predict toxicity and survival outcomes in patients receiving standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel.MethodsData were retrospectively collected from 113 r/r multiple myeloma patients treated between April 2021 and July 2022 across six international CAR-T centers. The HT score—composed of factors related to hematopoietic reserve and baseline inflammatory state—was determined prior to lymphodepleting chemotherapy.ResultsAt lymphodepletion, 63 patients were HTlow (score 0–1) and 50 patients were HThigh (score ≥ 2). Compared to their HTlow counterparts, HThigh patients displayed prolonged severe neutropenia (median 9 vs. 3 days, p < 0.001), an increased severe infection rate (40% vs. 5%, p < 0.001), and more severe ICANS (grade ≥ 3: 16% vs. 0%, p < 0.001). One-year non-relapse mortality was higher in the HThigh group (13% vs. 2%, p = 0.019) and was predominantly attributable to fatal infections. Response rates according to IMWG criteria were higher in HTlow patients (≥ VGPR: 70% vs. 44%, p = 0.01). Conversely, HThigh patients exhibited inferior progression-free (median 5 vs. 15 months, p < 0.001) and overall survival (median 10.5 months vs. not reached, p < 0.001).ConclusionsThese data highlight the prognostic utility of the CAR-HEMATOTOX score for both toxicity and treatment response in multiple myeloma patients receiving BCMA-directed CAR-T. The score may guide toxicity management (e.g. anti-infective prophylaxis, early G-CSF, stem cell boost) and help to identify suitable CAR-T candidates.