Morbidity In Patients Research Articles

The Influence of Surgical Complexity and Center Experience on Postoperative Morbidity After Minimally Invasive Surgery in Gynecologic Oncology: Lessons Learned from the ROBOGYN-1004 Trial.

This study was a secondary analysis of the ROBOGYN-1004 trial conducted between 2010 and 2015. The study aimed to identify factors that affect postoperative morbidity after either robot-assisted laparoscopy (RL) or conventional laparoscopy (CL) in gynecologic oncology. The study used two-level logistic regression analyses to evaluate the prognostic and predictive value of patient, surgery, and center characteristics in predicting severe postoperative morbidity 6 months after surgery. This analysis included 368 patients. Severe morbidity occurred in 49 (28 %) of 176 patients who underwent RL versus 41 (21 %) of 192 patients who underwent CL (p = 0.15). In the multivariate analysis, after adjustment for the treatment group (RL vs CL), the risk of severe morbidity increased significantly for patients who had poorer performance status, with an odds ratio (OR) of 1.62 for the 1-point difference in the WHO performance score (95 % CI 1.06-2.47; p = 0.027) and according to the type of surgery (p < 0.001). A focus on complex surgical acts showed significant more morbidity in the RL group than in the CL group at the less experienced centers (OR, 3.31; 95 % CI 1.0-11; p = 0.05) compared with no impact at the experienced centers (OR, 0.87; 95 % CI 0.38-1.99; p = 0.75). The findings suggest that the center's experience may have an impact on the risk of morbidity for patients undergoing complex robot-assisted surgical procedures.

Impact of post-operative infection on revision procedures in breast reconstruction: A marketscan database analysis

BackgroundEsthetic complications, such as capsular contracture and soft-tissue contour defects, hinder the desired outcomes of breast reconstruction. As subclinical infection is a prevailing theory behind capsular contracture, we investigated the effects of post-operative infections on these issues and revision procedures. MethodsWe conducted a retrospective database study (2007–2021) on breast reconstruction patients from the MarketScan® Databases. Esthetic complications were defined by their associated revision procedures and queried via CPT codes. Severe capsular contracture (Grade 3–4) was defined as requiring capsulotomy or capsulectomy with implant removal or replacement. Moderate and severe soft-tissue defects were determined by the need for fat grafting or breast revision, respectively. Generalized linear models were used, adjusting for comorbidities and surgical factors (p < 0.05). ResultsWe analyzed the data on 62,510 eligible patients. Post-operative infections increased the odds of capsulotomy (OR 1.59, p < 0.001) and capsulectomy (OR 2.30, p < 0.001). They also raised the odds of breast revision for severe soft-tissue defects (OR 1.21, p < 0.001). There was no significant association between infections and fat grafting for moderate defects. Patients who had post-operative infections were also more likely to experience another infection after fat grafting (OR 3.39, p = 0.0018). In two-stage reconstruction, infection after tissue expander placement was associated with greater odds of infection after implant placement. ConclusionPost-operative infections increase the likelihood of developing severe soft-tissue defects and capsular contracture requiring surgical revision. Our data reinforce the role of infections in the pathophysiology of capsular contracture. Additionally, infections elevate the risk of subsequent infections after fat grafting for moderate defects, further increasing patient morbidity.

Understanding Acute Pancreatitis in End-Stage Renal Disease: Unraveling etiologies, clinical presentations, management strategies, and complications: a narrative review

Acute pancreatitis (AP) is a common disease with defined diagnostic criteria, radiological findings, and management guidelines. Patients with end-stage renal disease (ESRD) are at an increased risk of developing AP. The diagnosis of AP in ESRD is challenging, and the clinical presentation may mimic other pathologies. Moreover, the impact of AP on the overall morbidity and mortality in ESRD patients warrants a tailored therapeutic approach. We conducted a literature search for published manuscripts on AP and ESRD up to November 2023 in several databases such as Google Scholar and PubMed, and employed the following search terms: “acute pancreatitis”, “pancreatitis”, “end-stage renal disease”, “hemodialysis”, “peritoneal dialysis”, “diagnostic criteria”, “etiology”, “presentation”, “management”, “complication”, “prognosis”, “mortality”. Qualitative and quantitative data were both extracted. This manuscript reviews current evidence-based literature about the etiology and clinical presentation of AP in ESRD. It sheds the light on the current clinical studies that reflect beneficial management strategies as well as complications of AP in ESRD. Patients with ESRD are more likely to develop AP and subsequently severe pancreatitis with high mortality rates compared to the general population. The etiology of AP in ESRD is multifactorial and management is focused on pain control, early nutritional support and most importantly maintaining a fluid balance. While existing research has shed light on certain aspects of AP in ESRD, additional literature focused on this topic is required to foster a deeper and broader understanding of AP in ESRD.

Postoperative outcomes of acute-on-chronic liver failure in infants and children with biliary atresia.

Acute-on-chronic liver failure (ACLF) is associated with increased mortality and morbidity in patients with biliary atresia (BA). Data on impact of ACLF on postoperative outcomes, however, are sparse. We performed a retrospective analysis of patients with BA aged <18 years who underwent LT between 2011 and 2021 at our institution. ACLF was defined using the pediatric ACLF criteria: ≥1 extra-hepatic organ failure in children with decompensated cirrhosis. Of 107 patients (65% female; median age 14 [9-31] months) who received a LT, 13 (12%) had ACLF during the index admission prior to LT. Two (15%) had Grade 1; 4 (30%) had Grade 2; and 7 (55%) had Grade ≥3 ACLF. ACLF cohort was younger at time of listing (5 [4-8] vs. 9 [6-24] months; p < .001) and at LT (8 [8-11] vs. 16 [10-40] months, p < .001) compared to no-ACLF group. Intraoperatively, ACLF patients had higher blood loss (40 [20-53] vs. 10 [6-19] mL/kg; p < .001) and blood transfusion requirements (33 [21-69] vs. 18 [7-25] mL/kg; p = .004). Postoperatively, they needed higher vasopressor support (31% vs. 10.6%; p = .04) and had higher total hospital length of stay (106 [45-151] vs. 13 [7-30] days; p = .023). Rate of return to the operating room, hospital readmission rates, and 1-year post-LT survival rates were comparable between the groups. Despite higher perioperative complications, survival outcomes for ACLF in BA after LT are favorable and comparable to those without ACLF. These encouraging data reiterate prioritization during organ allocation of these critically ill children for LT.

Transjugular Intrahepatic Portosystemic Shunt as a Bridge to Abdominal Surgery in Cirrhosis.

Abdominal surgery is associated with high postoperative mortality and morbidity in cirrhotic patients. Despite improvements in surgical techniques, clinical management, and intensive care, the outcome could be influenced by the degree of portal hypertension, the severity of hepatopathy, or the type of surgery. Preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement, in addition to medical therapy, plays an important role in managing the complications of portal hypertension such as ascites, hepatic encephalopathy, variceal bleeding or portal vein thrombosis. To date, the improvement of post-surgery outcomes in cirrhotic patients after TIPS placement remains unclear. Only observational data existing in the literature and prospective studies are urgently needed to evaluate the efficacy and safety of TIPS in this setting. This review aims to outline the role of TIPS as a tool in postoperative complications reduction in cirrhotic patients, both in the setting of emergency and elective surgery.

Morbidity and mortality in premature or low birth weight patients with congenital heart disease in three European pediatric heart centers between 2016 and 2020.

The treatment of preterm and low birth weight (LBW) neonates born with congenital heart disease (CHD) requiring early cardiac intervention remains challenging. We aimed to analyze morbidity and mortality in this combined high-risk patient group. A retrospective cohort study was conducted of preterm [<37 weeks gestational age (GA)] and/or LBW neonates (<2,500 g) born with a diagnosis of CHD, which requires invasive cardiac intervention (surgery or catheter) within their first year of life. Patients born between 2016 and 2020 and treated in three European pediatric heart centers were included. A total of 308 neonates (51% male) with CHD were included. Of those, 237 (77%) were born preterm, 259 (84%) were LBW, and 188 (61%) were both. The median GA was 35.4 weeks (interquartile range 33.3-36.9) and the mean birth weight was 2,016 ± 580 g. CHD was categorized as simple (12%), moderate (64%), or severe (24%). The overall complication rate was 45% and was highest in patients with severe CHD (p = 0.002). One-year mortality (19%) was associated with severe CHD, low relative birth weight in patients with genetic diagnoses, and low GA at birth, whereas GA at birth significantly impacted survival only after 3 months of life. The high morbidity and mortality in preterm and LBW neonates with CHD reflect their complexity and consequent limited treatment feasibility.

Comparative analysis of linear- and circular-stapled gastrojejunostomies in Roux-en-Y gastric bypass: a focus on postoperative morbidity using the comprehensive complication index

PurposeThe linear-stapled (LSA) and the circular-stapled anastomosis (CSA) are the two most commonly performed techniques for the gastrojejunostomy (GJ) during laparoscopic Roux-en-Y gastric bypass (RYGB). This study compared the outcome after both techniques with special focus on postoperative morbidity using the comprehensive complication index (CCI).MethodsFive hundred eighty-eight patients operated between 01/2010 and 12/2019 were included in the final analysis and divided in two cohorts according to the surgical technique of the GJ (LSA (n = 290) or CSA (n = 298)). Before 09/2016, the CSA was exclusively performed for the GJ, while after 09/2016, the LSA was solely used.ResultsThe mean CCI for patients with Clavien-Dindo complication grade ≥ 2 within the first 90 days after RYGB was 31 ± 9.1 in the CSA and 25.7 ± 6.8 in the LSA group (p < 0.001), both values still below the previously published benchmark cutoff (≤ 33.73). The C-reactive Protein (CRP)-levels on postoperative days (POD) 1 and 3 as well as the use of opioids on POD 1 were significantly higher in the CSA- than in the LSA-group (all p < 0.001). There were significantly more internal herniations in the CSA group during the first 24 postoperative months (p < 0.001).ConclusionPatients after RYGB with CSA were found to have higher CCI values during the first 90 PODs compared to patients in which the LSA was applied. To achieve optimal outcomes in terms of patient morbidity, the LSA seems to be the superior technique for GJ in RYGB.

Should Soldiers Take Oral Tranexamic Acid Before Going into Battle?

Tranexamic acid is an inexpensive antifibrinolytic treatment that reduces morbidity and mortality in civilian and military trauma patients. It must be administered within 3 hours of the injury, and its efficacy is greater the earlier it is given. It is already used preventively in the civilian environment in a number of indications to reduce bleeding and bleeding-related mortality. We wondered about the potential benefits of preventive oral administration of tranexamic acid prior to an assault for military personnel with a potential risk of injury.

The Safety of Glycopeptide-Impregnated Calcium Sulphate Following Debridement, Antibiotics and Implant Retention (DAIR) for Infected Total Knee Replacement.

Background and objective The impact of prosthetic joint infection (PJI) stretches far beyond the physical nature of the disease. It can result in psychological and social consequences, with significant morbidity and mortality for patients. Calcium sulphate-based delivery agents are effective in the management of PJI, yet with associated risks of systemic adverse events. This study aims to evaluate the risk of systemic adverse events when using calcium-sulphate-based local antibiotic delivery agents in the management of PJIs. Methodology We identified 43 patients who underwent debridement, antibiotics and implant retention (DAIR) for infected total knee arthroplasty (TKA) between 2008 and 2014. Patients in the control groupunderwent conventional intravenous and then oral antibiotic administration, while those in the intervention groupunderwent additional local antibiotic therapy via a calcium sulphate alpha hemihydrate matrix. Case notes and laboratory results data were compiled to establish the safety and efficacy of local glycopeptide delivery. Results Serum vancomycin levels were within the safe therapeutic range for all patients in the intervention group with no difference in serum assays between treatment groups (intervention 7.7 mg/L; control 8.0 mg/L; P = 0.85). Renal function for the study cohort improved at every time point post-operatively when referenced against pre-operative renal function (P < 0.05). There was no difference in renal function between intervention and control groups on day 1, one week, six weeks or 12 weeks post-operatively (P = 0.78, 0.89, 0.20 and 0.50). Conclusions Local glycopeptide delivery via a calcium sulphate alpha hemihydrate matrix did not result in systemic adverse consequences specifically not raising the systemic level of glycopeptide, nor reducing renal function. Implications for future research Although demonstrates a safety profile and potential therapeutic benefit, the long-term efficacy of this approach needs to be established. Importantly, selection bias may contribute to masking clinically significant differences in post-operative outcomes.

The Impact of Social Determinants of Health in the Morbidity of Patients with Huntington Disease (P6-3.001)

The Impact of Social Determinants of Health in the Morbidity of Patients with Huntington Disease (P6-3.001)

Early safety outcomes of laparoscopic one anastomosis gastric bypass in patients with class III, IV, and V obesity.

The extremely obese patient deserves special consideration: significant comorbidities, technical difficulties, and increased postoperative morbidity and mortality are all expected in this patient population. The study compared early postoperative complications (≤30-day) following one-anastomosis gastric bypass (OAGB) morbidity in patients with morbid obesity class IV obesity, body mass index (BMI) ≥50-59.9kg/m2, and class V obesity, BMI ≥60 patients. We retrospectively reviewed perioperative OAGB outcomes in three BMI groups. Operative time, length of stay (LOS), and overall early postoperative complication rates were studied. Patient-reported complications were ranked by Clavien-Dindo Classification (CDC). Between January 2017-December 2021, consecutive patients with obesity class III (n=2950), IV (n=256), and V (n=23) underwent OAGB. BMI groups were comparable in sex, age, and associated comorbidities. Mean operative time was significantly longer in the higher BMI groups: class III (66.5±25.6min), IV (70.5±28.7min), and V (80.0±34.7min), respectively (p=0.018); no difference in LOS. In respective BMI classes, ≤30-day complication rates were 3.2%, 3.5%, and 4.3% (p=0.926). The respective number of patients with CDC grades of one to two were 45 (1.5%), 6 (2.3%), and 1 (4.3%), p=0.500; and in grade ≥3a, 25 (0.8%), 1 (0.4%), 0 (0.0%), p=0.669. There was 0.06% mortality (n=2 in 3229), both in BMI class III. OAGB is a safe BS procedure in patients with class III, IV, and V obesity in the perioperative term with comparable ≤30-day morbidity in the three BMI groups.

Factors Associated With Physical Inactivity of Recipients of a Kidney Transplant: Results From the ADHERE BRAZIL Multicenter Study.

Physical activity is recommended for recipients of a kidney transplant. However, ADHERE BRAZIL study found a high prevalence (69%) of physical inactivity in Brazilian recipients of a kidney transplant. To tackle this behavior, a broad analysis of barriers is needed. This study aimed to identify factors (patient and transplant center levels) associated with physical inactivity among recipients of a kidney transplant. This was a subproject of the ADHERE BRAZIL study, a cross-sectional, multicenter study of 1105 recipients of a kidney transplant from 20 kidney transplant centers. Using a multistage sampling method, patients were proportionally and randomly selected. Applying the Brief Physical Activity Assessment questionnaire, patients were classified as physically active (≥150min/wk) or physically inactive (<150min/wk). On the basis of an ecological model, 34 factors associated with physical inactivity were analyzed by sequential logistic regression. At the patient level, physical inactivity was associated with smoking (odds ratio = 2.43; 95% CI = 0.97-6.06), obesity (odds ratio = 1.79; 95% CI = 1.26-2.55), peripheral vascular disease (odds ratio = 3.18; 95% CI = 1.20-8.42), >3 posttransplant hospitalizations (odds ratio = 1.58; 95% CI = 1.17-2.13), family income of >1 reference salary ($248.28 per month; odds ratio = 0.66; 95% CI = 0.48-0.90), and student status (odds ratio = 0.58; 95% CI = 0.37-0.92). At the center level, the correlates were having exercise physiologists in the clinical team (odds ratio = 0.54; 95% CI = 0.46-0.64) and being monitored in a teaching hospital (undergraduate students) (odds ratio = 1.47; 95% CI = 1.01-2.13). This study identified factors associated with physical inactivity after kidney transplantation that may guide future multilevel behavioral change interventions for physical activity. In a multicenter sample of recipients of a kidney transplant with a prevalence of physical inactivity of 69%, we found associations between this behavior and patient- and center-level factors. At the patient level, the chance of physical inactivity was positively associated with smoking, obesity, and patient morbidity (peripheral vascular disease and hospitalization events after kidney transplantation). Conversely, a high family income and a student status negatively correlated with physical inactivity. At the center level, the presence of a dedicated professional to motivate physical activity resulted in a reduced chance of physical inactivity. A broad knowledge of barriers associated with physical inactivity can allow us to identify patients at a high risk of not adhering to the recommended levels of physical activity.

The role of Matrix Metalloproteinase-2 and Galectin-3 as predictive biomarkers for all-cause mortality in patients undergoing transfemoral transcatheter aortic valve implantation

Background Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. Methods Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. Results The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan–Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). Conclusions In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.

Sapovirus: an emerging pathogen in kidney transplant recipients?

Diarrhea is an important cause of morbidity and mortality in immunocompromised patients. After including sapovirus to the viral gastroenteritis screening of our institution's laboratory, we noticed an increase in sapovirus infections among kidney transplant recipients. Therefore, we assumed former gastrointestinal tract infections with unidentified pathogens could have been caused by sapovirus. To better understand the characteristics of a sapovirus infection in a high-risk group we initiated this study. Over a period of 6months, all transplant recipients with diarrhea and later identified viral/unknown pathogens were included. Kidney function, levels of immunosuppressants and c-reactive protein, acid-base balance, onset of symptoms and time of hospitalization were analyzed. Among 13 hospitalized kidney transplant recipients sapovirus was detected in four patients, while in the remaining nine, three were diagnosed with norovirus, one with cytomegalovirus, one with inflammatory bowel disease and in four patients no pathogen was identified. Even though statistically not significant, creatinine levels at admission tended to be higher in sapovirus patients (median: sapovirus: 3.3mg/dl (1.3; 5.0), non-sapovirus: 2.5mg/dl (1.1; 4.9), p = 0.710). Also, Tacrolimus levels showed the same trend (sapovirus: 13.6ng/ml (12.9; 13.6), non-sapovirus: 7.1ng/ml (2.6; 22.6), p = 0.279). On discharge creatinine levels improved equally in both groups (sapovirus: 1.7mg/dl (1.4; 3.2), non-sapovirus: 2mg/dl (1.0; 3.6), p = 0.825). In high-risk patients, early symptomatic treatment remains crucial to protect the transplant`s function. In our cohort all patients recovered well. Larger cohorts and longer follow-up times are needed to detect the long-term consequences and a potential need for further research regarding specific treatment. The study has been registered on DRKS (trialsearch.who.int), Reg. Nr. DRKS00033311 (December 28th 2023).

Advancing the Diagnosis of Periprosthetic Joint Infections: Integrated Microfluidic Platform for Alpha-Defensins-Specific Aptamer Selection and Its Analytical Applications.

Periprosthetic joint infections (PJIs) pose a significant challenge in orthopedic surgery, particularly total joint arthroplasty (TJA), due to the potential for implant failure and increased patient morbidity. Early and accurate detection of PJIs is crucial for timely intervention and better patient prognosis. Herein, we successfully screened a high-affinity aptamer targeting alpha-defensin complex human neutrophil protein 1-3 (HNP 1-3; potential PJI biomarkers in synovial fluid [SF]) for the first time using systematic evolution of ligands by exponential enrichment (SELEX) on an integrated microfluidic platform. The compact microfluidic device enabled efficient screening, with each round completed within <2 h, comprising five rounds of positive selection, two rounds of negative selection, and one round of competitive selection. A novel one-aptamer-one-antibody assay was further developed from the optimal aptamer screened, and it could accurately quantify HNP 1-3 in SF within 3 h with only ∼50 μL of SF. The assay demonstrated strong binding affinity and specificity for the target protein in SF. Thirteen PJI SF samples were accurately diagnosed and the assay was accurate over a wide dynamic range (0.32-100 mg/L). This study has showcased a rapid and accurate diagnostic tool for PJI detection, which should see widespread use in the clinic, holding promise for potential analytical applications in orthopedic surgery and improving patient care.

Synthesis and evaluation of a novel vancomycin-infused, biomimetic bone graft using a rat model of spinal implant-associated infection

BackgroundPostoperative infection is a complication of spinal fusion surgery resulting in increased patient morbidity. Strategies including intraoperative application of powdered vancomycin have been proposed to reduce the incidence of infection; however, such antimicrobial effects are short-lived. MethodsInstrumentation of the L4–L5 vertebrae was performed mimicking pedicle screw and rod fixation in 30 rats. Titanium instrumentation inoculated with either PBS or 1×105 CFU bioluminescent MRSA, along with biomimetic bone grafts infused with varying concentrations of vancomycin and 125 µg of rhBMP-2 (BioMim-rhBMP-2-VCM) were implanted prior to closure. Infection was quantified during the six-week postoperative period using bioluminescent imaging. Arthrodesis was evaluated using micro-CT. ResultsInfected animals receiving a bone graft infused with low-dose (0.18 mg/g) or high-dose vancomycin (0.89 mg/g) both exhibited significantly lower bioluminescent signal over the six-week postoperative period than control animals inoculated with MRSA and implanted with bone grafts lacking vancomycin (p=.019 and p=.007, respectively). Both low and high-dose vancomycin-infused grafts also resulted in a statistically significant reduction in average bioluminescence when compared to control animals (p=.027 and p=.047, respectively), independent of time. MicroCT analysis of animals from each group revealed pseudoarthrosis only in the control group, suggesting a correlation between infection and pseudoarthrosis. MRSA-inoculated control animals also had significantly less bone volume formation on micro-CT than the PBS-inoculated control cohort (p<.001), the MRSA+low-dose vancomycin-infused bone graft cohort (p<.001), and the MRSA+high-dose vancomycin-infused bone graft cohort (p<.001). ConclusionBioMim-rhBMP-2-VCM presents a novel tissue engineering approach to simultaneously promoting arthrodesis and antimicrobial prophylaxis in spinal fusion. Despite mixed evidence of potential osteotoxicity of vancomycin reported in literature, BioMim-rhBMP-2-VCM preserved arthrodesis and osteogenesis with increasing vancomycin loading doses due to the graft's osteoinductive composition.

Loading-Dose Dupilumab May Function as a Prophylactic Agent for Food-Induced Anaphylaxis: A Case and Review of the Literature

Recent advances in targeted therapy using monoclonal antibodies have revolutionized care in many fields, and dupilumab for the treatment of moderate-severe atopic dermatitis is no exception. While on a trial of loading dose dupilumab, a 25-year-old white male with a past medical history significant for anaphylaxis after ingesting peanuts and tree nuts did not experience anaphylaxis after accidentally consuming almonds. Similarly to anti-IgE, the large-scale inhibition of IL-4 and IL-13 signaling to various immune cells involved with type II hypersensitivity reactions using loading dose dupilumab may have played a role in preventing anaphylaxis in this patient. The role of loading dose dupilumab as a potential prophylactic agent against food-induced anaphylaxis could be explored cautiously as a novel way to reduce both morbidity and mortality in patients with these allergies.

Cardiovascular Morbidity in Systemic Lupus Erythematosus: A Single-Center Retrospective Study.

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory condition affecting multiple systems. Cardiovascular morbidity is a significant concern, with around 25% of SLE patients experiencing cardiac complications. This study aims to determine the prevalence of cardiovascular morbidity in SLE patients in King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. This retrospective record-based research was conducted at KFMC from January 2015 to October 2023. A review of the medical files of all SLE patients was accomplished. The vast majority of the patients (90.9%) were females. The mean age for the patients was 36.5 years. The most common comorbidities were lupus nephritis (34.6%), hypothyroidism (18.4%), and anti-phospholipid syndrome (9.2%). The most commonly used medications were hydroxychloroquine (81.8%), corticosteroids (prednisolone) (43.0%), and mycophenolate mofetil (27.9%). Around 45.2% (n= 176) of the patients with SLE developed cardiovascular complications. The most commonly reported cardiovascular diseases that developed after diagnosing patients with SLE were hypertension (22.4%), valvular heart diseases (13.2%), and dyslipidemia (9.2%). The study also found that anti-dsDNA antibodies can reduce the likelihood of developing hypertension by 40%. This research contributes to the medical literature on SLE and sets the stage for future research on personalized healthcare strategies for managing SLE and its complications. This study highlights that a considerable proportion of SLE patients(~50%) develop cardiovascular complications, with hypertension, valvular heart diseases, and dyslipidemia being the most common. We also discovered that anti-double-stranded deoxyribonucleic acid antibodies (Anti-dsDNA) reduce the likelihood of developing hypertension.

Abstract CT080: A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma

Abstract Background: Local tumor progression is a cause of significant mortality and morbidity in patients (pts) with inoperable pancreatic ductal adenocarcinoma (PDAC). Effective approaches to achieve durable local control are urgently needed. Metabolic reprogramming and enhanced mitochondrial function are known contributors to chemo- and radio-resistance in PDAC. CPI-613, a lipoic acid analog that selectively inhibits components of the Krebs cycle in tumors, showed promising preclinical synergy in combination with gemcitabine and radiation (gem-RT). We initiated a phase I study (NCT05325281) to determine the maximum tolerated dose (MTD) of CPI-613 when used with gem-RT. Here, we present the results from the first cohort of this study. Methods: Adult pts with inoperable PDAC that, by institutional multidisciplinary review, were considered to benefit from definitive local control of the primary tumor were eligible for the study. CPI-613 was administered once weekly by intravenous infusion over ~ 2 hours at a starting dose of 500 mg/m2 and dose-escalated using a Bayesian optimal interval design. Gemcitabine was given once weekly at 400 mg/m2 and RT at 45-54 Gray (Gy) in 25-30 fractions. Results: By Jan 7, 2024, six pts were enrolled, and five completed the treatment and dose-limiting toxicity (DLT) period. Table 1 describes the characteristics of these five pts. As CPI-613 was not associated with any additional toxicities, specifically cytopenia(s), after the first two pts, the study protocol was amended to allow CPI-613 to be administered on weeks gemcitabine was held for cytopenia(s). The study, therefore, enrolled five pts in the first cohort. All pts received ≥ 16 weeks of systemic chemotherapy with at least stable disease per imaging prior to enrollment. None of the pts experienced DLTs. All treatment-related toxicities were expected from gem-RT, unrelated to CPI-613, and manageable. The trial is currently enrolling pts in the second cohort (CPI-613 dose of 1000 mg/m2). Conclusions: CPI-613 combined with gem-RT was safe and well tolerated at a dose of 500 mg/m2. Recruitment to the study is ongoing to determine the MTD of CPI-613 in combination with gem-RT. Table 1. Characteristic of Patients Sex Race Age ECOG Stage Prior chemotherapy Chemotherapy duration (weeks) M W 67 1 LA FFX 16 M W 64 1 LA GnP 35 M W 73 1 BR* GnP 16 M B 71 1 LA GnP 27 M W 80 1 Oligometastatic** GnP 18 * Medically inoperable ** Two lung metastases treated with stereotactic body radiation therapy (SBRT); BR: Borderline resectable; B: Black; FFX: FOLFIRINOX; GnP: Gemcitabine/Nab-paclitaxel; LA: Locally advanced. M: Male; W: White Citation Format: Mandana Kamgar, Husain Yar Khan, Amro Aboukameel, Sahar F. Bannoura, Brian Y. Chung, Aniko Szabo, Yiwei Li, Mohammed Najeeb Al Hallak, Philip A. Philip, Ben George, Kathleen K. Christians, Douglas B. Evans, Susan Tsai, Beth Erickson, John M. Goldberg, Asfar S. Azmi, William A. Hall. A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT080.

A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country

BackgroundThe commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location.ObjectiveThis study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors.MethodIn this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines.ResultsOne thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36–66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function.Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001).ConclusionAKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.