Primary Therapeutic Option Research Articles

Thirty-day mortality risk in patients following radiofrequency and cryoballoon ablation for atrial fibrillation across the entire nation of Poland: An 8-year analysis from the National Health Fund of Poland.

Atrial fibrillation (AF) is the most common sustained arrhythmia, and catheter ablation (CA) is a primary therapeutic option. However, the 30-day all-cause mortality risk associated with CA for AF may be underestimated due to selection bias. Our study aimed to assess 30-day mortality in an unselected cohort of patients. Data from the National Health Fund-Poland covered over 99% of nationwide radiofrequency ablation (RF) or cryoballoon ablation for AF, with 100% recorded deaths. The study included consecutive CA procedures in adult patients between 2012 and 2019. Thirty-day mortality rates were calculated for each age group. A total of 31 214 CAs for AF were performed on 26 767 patients (34.8% female). Forty-four percent of patients had hypertension, 31.2% had coronary artery disease, 14.4% had heart failure, 11% had diabetes mellitus, 5.6% had malignant neoplasms, 2.7% had a previous myocardial infarction, 2.5% had a previous stroke, and 2.2% had kidney disease. Thirty-two deaths (0.1%) occurred within 30 days, with the highest mortality in the oldest age group (>80 years). Statistical analysis revealed higher incidences of kidney disease (p < 0.001) and heart failure (p = 0.001) in patients who died within 30 days. Mortality risk did not significantly differ between cryoballoon and RF ablation, as well as first and subsequent ablation for AF. The risk of death within 7 days postablation for AF was 1 in 2750 procedures, while the risk of death on the same day postablation was 1 in 6250 procedures. The 30-day mortality rate in a large, unselected AF ablation cohort, covering 99% of procedures in the country, is low except for the oldest patients. This factor should be taken into consideration when offering CA for AF.

Propofol versus Dexmedetomidine for Sedation of Cancer Patients Undergoing Endoscopic Retrograde Cholangiopancreatography: Randomized Single-Blinded Controlled Study

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a primary diagnostic and therapeutic option for pancreaticobiliary pathologies. Objectives: This study aimed to investigate the efficacy and safety of dexmedetomidine versus propofol during ERCP in cancer patients. Methods: This randomized controlled single-blinded trial was conducted with 202 cancer patients aged 21 to 60 years, of both sexes, with a body mass index of 18.5 to 30 kg/m2, and classified as American Society of Anesthesiologists (ASA) class II - III, who were undergoing ERCP. The patients were randomly assigned to two equal groups. The Propofol Group (n = 101) received a loading dose of propofol (1 - 2 mg/kg over 30 seconds) followed by an infusion (0.05 - 0.1 mg/kg/hour). The Dexmedetomidine Group (n = 101) received a loading dose of dexmedetomidine (1 μg/kg over 10 minutes) followed by an infusion (0.2 - 0.7 μg/kg/hour). The maintenance dose was adjusted during the procedure based on vital signs, Bispectral Index (BIS), and oxygen saturation. Results: The Dexmedetomidine group showed a significantly lower incidence of intra-procedural hypoxemic events (14.9% vs. 26.7%, P = 0.037) and a comparable incidence of hypotension (17.8% vs. 13.9%, P = 0.441). Dexmedetomidine also demonstrated significantly lower intraoperative pain scores according to the Facial Pain Score (P &lt; 0.05), significantly lower postoperative Visual Analog Scale (VAS) scores (P &lt; 0.05), and a lower frequency of postoperative nausea and vomiting (PONV) compared to the Propofol group. Additionally, there was a significantly higher frequency of endoscopist satisfaction in the Dexmedetomidine group compared to the Propofol group (P &lt; 0.05). Conclusions: Dexmedetomidine can be used as a safe and effective alternative to propofol for deep sedation of cancer patients undergoing ERCP. It is associated with a lower incidence of hypoxemic events, effective intraoperative sedation, quicker recovery, and superior analgesic effects both intraoperatively and postoperatively compared to propofol.

Tuberous Sclerosis Complex and the kidneys: what nephrologists need to know.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives.

Mesothelin expression correlates with elevated inhibitory immune activity in patients with colorectal cancer

The expression of the protein Mesothelin (MSLN) is highly variable in several malignancies, including colorectal cancer (CRC), and high levels are associated with aggressive clinicopathological features and worse patient survival. Colorectal cancer is both a common and deadly cancer; being the third most common in incidence and second most common cause of cancer-related death. While systemic therapy remains the primary therapeutic option for most patients with stage IV (metastatic; m) CRC, their disease eventually becomes treatment refractory, and 85% succumb within 5 years. Microsatellite-stable (MSS) CRC tumors, which constitute more than 90% of patients with mCRC, are generally refractory to immunotherapeutic interventions. In our current work, we characterize MSLN levels in CRC, specifically correlating expression with clinical outcomes in relevant CRC subtypes, and explore how MSLN expression impacts the status of immune activation and suppression in the peritumoral microenvironment. Higher MSLN expression is prevalent in CMS1 and CMS4 CRC subtypes and correlates with higher gene mutation rates across the patient cohorts. Further, MSLN-high patients exhibit increased M1/M2 macrophage infiltration, PD-L1 staining, immune-inhibitory gene expression, enrichment in inflammatory, TGF-β, IL6/JAK/STAT3, IL2/STAT5 signaling pathways, and mutation in KRAS and FBXW7. Together, these results suggest that MSLN protein is a potential target for antigen-specific therapy and supports investigation into its tumorigenic effects to identify possible therapeutic interventions for patients with high MSLN expressing MSS CRC.

IL-10 Is Critical for Regulation of Cytotoxic CD4+NKG7+ T Cells in Lung Allograft Rejection but Is Not Required for Allograft Acceptance.

Lung transplant remains the primary therapeutic option for patients with end-stage lung disease, but long-term survival rates remain suboptimal compared with other solid organ transplants. Acute cellular rejection (ACR) is a significant challenge in lung transplant recipients, with T cell-mediated mechanisms playing a major role. IL-10 is known for its immunoregulatory function, although its specific role in lung allograft rejection remains unclear. Using the mouse orthotopic lung transplant model, we investigated the role of IL-10 in regulating alloeffector T cell responses. Unexpectedly, we found that IL-10 was not required for early costimulation blockade-induced allograft acceptance. However, IL-10 deficiency or blockade resulted in increased CD4+ T cell numbers, proliferation, graft infiltration, and alloeffector responses. In the absence of IL-10, CD4+ T cell responses predominated over CD8 responses during ACR in contrast to wild-type mice. Type 1 immunity (IFN-γ) responses along with elevated CD4+NKG7+ and CD4+CD107a+ responses predominated during ACR, highlighting a critical regulatory role for IL-10 in modulating CD4+ T cell alloimmune responses. We further demonstrated increased colocalization of NKG7 and CD107a in CD4+ T cells from IL-10-deficient allografts, suggesting coordination in cytotoxic activity. Together, our findings highlight a critical role for IL-10 in regulation of cytotoxic CD4+NKG7+ T cells, an effector population that needs further investigation to elucidate their role in lung allograft rejection.

Regression of an ALK-Negative Cerebral Inflammatory Myofibroblastic Tumour by Steroid Therapy: A Case Report and Literature Review

Introduction: Inflammatory myofibroblastic tumours (IMTs) are non-neoplastic lesions characterized by collagenous stroma and polyclonal mononuclear infiltrates. IMTs typically arise in the lung, retroperitoneum or abdominal region but rarely in the central nervous system (CNS). The primary therapeutic option is surgical resection, and other therapies are currently controversial. Case report: We report a case of 23-year-old male ALK-negative cerebral IMT patient from Han population via steroid therapy. No relapse is observed at the follow-up visit. Conclusion: These results support the role of internal medication and promote the use of personalized therapy in genome-profiled IMTs.

Cardiac amyloidosis and aortic stenosis: what do we know?

Aortic valve stenosis and cardiac amyloidosis, particularly transthyretin-related, often coexist and share a common clinical and demographic profile. Several pathophysiological hypotheses have been proposed regarding the causes of this association, neither of which fully substantiated in practice. The key to detect the coexistence of cardiac amyloidosis and aortic valve stenosis lies in clinical suspicion. It is possible to hypothesize concurrent cardiac amyloidosis in patients with aortic valve stenosis with the aid of clinical, electrocardiographic, echocardiographic, and extracardiac "red flags". Subsequent non-invasive diagnostic steps are often sufficient to establish a definitive diagnosis. The early diagnosis of this condition is pivotal since the presence of dual pathology worsens patient's prognosis, especially without intervention. Available data on treatment show a better outcome in terms of survival and cardiovascular events in patients undergoing percutaneous correction of valvular heart disease rather than medical therapy alone, regardless of the presence of cardiac amyloidosis. Furthermore, it seems that cardiac amyloidosis does not impact survival after transcatheter aortic valve replacement, even if higher rates of rehospitalizations have been described. Indeed, percutaneous treatment of valvular heart disease is currently considered the primary therapeutic option. Subsequently a disease-modifying treatment for transthyretin amyloidosis may be considered in order to delay disease progression and improve outcomes, even if specific data are still lacking.

Exploring the Awareness of Exercise Benefits among Women with Polycystic Ovarian Syndrome-A Cross-sectional Study

Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. With its increasing prevalence, it is crucial to emphasize effective preventative measures for a healthier life. Exercise is recognized as a primary therapeutic option for managing PCOS. Therefore, increasing awareness of the benefits of exercise among women is essential, as higher awareness is likely to lead to better outcomes through increased participation. This study aims to assess exercise awareness as a treatment option among females diagnosed with PCOS and evaluate the frequency of participation in exercise programs in Karachi. Methodology: This cross-sectional study involved 100 females diagnosed with PCOS who were visiting various government and private hospitals in Karachi, aged 18-35 years. Pregnant women and those with thyroid diseases were excluded. Data was collected using a self-designed questionnaire. The association between exercise awareness and participation was evaluated using the Chi-square test with SPSS version 20, and frequencies and percentages of qualitative variables were calculated. Results: 66% of females were aware of the benefits of exercise, with gynecologists being their primary source of information (60.6%). 67% of females were engaged in exercise, with 42 of them preferring walking. Additionally, 72% of females reported different barriers to exercise. The association between exercise awareness and participation was highly significant (p=0.00). Conclusion: Exercise training is crucial for managing PCOS. However, there needs to be more physical therapists as a critical source of information on exercise benefits for PCOS and in organizing related exercise programs. Keywords: Awareness, Exercise, Obesity, Polycystic Ovarian Syndrome.

Paradigm Shifts in Hodgkin Lymphoma Treatment: From Frontline Therapies to Relapsed Disease.

Combination chemotherapy with or without radiation has served as the primary therapeutic option for classic Hodgkin lymphoma (cHL), leading to durable remission in a majority of patients with early- and advanced-stage cHL. Patients with relapsed/refractory (RR) cHL could still be cured with salvage chemotherapy and autologous stem-cell transplantation. Brentuximab vedotin (BV) and the anti-PD-1-blocking antibodies, nivolumab and pembrolizumab, are highly effective treatments for cHL and have revolutionized the management of the disease. Recent studies incorporating BV and PD-1 blockade into salvage therapy for RR cHL and into frontline treatment regimens have changed the cHL treatment paradigm. The novel agents are also useful in the treatment of older patients who have poor outcomes with traditional therapy. This manuscript will review current strategies for approaching the management of previously untreated, RR, and challenging populations with cHL, including how to incorporate the novel agents.

Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma

The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. LR, PRFA, or TACE. Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation.

Historically, heparin has had the longest historical use as an anticoagulant and continues this day to be the primary therapeutic option for preventing thrombosis and thromboembolism in critically ill hospitalized patients. Heparin is also used to treat sepsis and sepsis-associated disseminated intravascular coagulation (DIC) in various countries. However, the efficacy and safety of heparin for this indication remains controversial, as adequately powered randomized clinical studies have not demonstrated as yet a survival benefit in sepsis and sepsis-associated DIC, despite meta-analyses and propensity analyses reporting improved outcomes without increasing bleeding risk. Further, activated protein C and recombinant thrombomodulin showed greater improvements in outcomes compared with heparin, although these effects were inconclusive. In summary, further research is warranted, despite the ongoing clinical use of heparin for sepsis and sepsis-associated DIC. Based on Japanese guidelines, antithrombin or recombinant thrombomodulin may be a preferable choice if they are accessible.

Changes in aorta hemodynamics in Left-Right Type 1 bicuspid aortic valve patients after replacement with bioprosthetic valves: An in-silico study.

Bicuspid aortic valve (BAV) is the most common cardiac congenital abnormality with a high rate of concomitant aortic valve and ascending aorta (AAo) pathologic changes throughout the patient's lifetime. The etiology of BAV-related aortopathy was historically believed to be genetic. However, recent studies theorize that adverse hemodynamics secondary to BAVs also contribute to aortopathy, but their precise role, specifically, that of wall shear stress (WSS) magnitude and directionality remains controversial. Moreover, the primary therapeutic option for BAV patients is aortic valve replacement (AVR), but the role of improved post-AVR hemodynamics on aortopathy progression is also not well-understood. To address these issues, this study employs a computational fluid dynamics model to simulate personalized AAo hemodynamics before and after TAVR for a small cohort of 6 Left-Right fused BAV patients. Regional distributions of five hemodynamic metrics, namely, time-averaged wall shear stress (TAWSS) and oscillating shear index (OSI), divergence of wall shear (DWSS), helicity flux integral & endothelial cell activation potential (ECAP), which are hypothesized to be associated with potential aortic injury are computed in the root, proximal and distal ascending aorta. BAVs are characterized by strong, eccentric jets, with peak velocities exceeding 4 m/s and axially circulating flow away from the jets. Such conditions result in focused WSS loading along jet attachment regions on the lumen boundary and weaker, oscillating WSS on other regions. The jet attachment regions also show alternating streaks of positive and negative DWSS, which may increase risk for local tissue stretching. Large WSS magnitudes, strong helical flows and circumferential WSS have been previously implicated in the progression of BAV aortopathy. Post-intervention hemodynamics exhibit weaker, less eccentric jets. Significant reductions are observed in flow helicity, TAWSS and DWSS in localized regions of the proximal AAo. On the other hand, OSI increases post-intervention and ECAP is observed to be low in both pre- and post-intervention scenarios, although significant increases are also observed in this ECAP. These results indicate a significant alleviation of pathological hemodynamics post AVR.

Hyperparathyroidism and Peripheral Arterial Disease.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

Efficacy of esophageal stents as a primary therapeutic option in spontaneous esophageal perforations: a systematic review and meta-analysis of observational studies.

Spontaneous esophageal perforation traditionally mandates urgent surgical treatment. Lately, esophageal stents have been used to reduce the associated morbidity and mortality. The current systematic review aimed to assess the efficacy of stents as a primary treatment option in this scenario. A systematic search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library for studies published in the English language between 2000 and 2023. We included observational studies reporting on the use of stents, alongside conservative measures and drainage procedures, in patients with spontaneous esophageal perforations. Primary outcomes were sealing rate (persistent leak occlusion) and failure rate (mortality or conversion to a major surgical operation). Secondary outcomes included patients' presentation, sepsis, drainage procedures, and reinterventions. Results for primary outcomes were presented as pooled rates with 95% confidence intervals (CIs), using a random-effects model. Methodological quality was assessed using the MINORS score. Eighteen studies involving 171 patients were included. Sealing rate was 86% (95%CI 77-93%) and failure rate was 14% (95%CI 7-22%). Weighted mortality rate was 6% (95%CI 2-13%), while conversion to surgical treatment was 2% (95%CI 0-9%). Late presentation was not related to a statistically significant increase in treatment failure (odds ratio 1.85, 95%CI 0.37-9.30; P=0.72). Drainage procedures were required for the majority of patients, with a high rate of surgical and endoscopic reinterventions. Our results imply that stents may offer an effective and safe alternative treatment for patients with spontaneous esophageal perforations. Additional endoscopic and surgical drainage procedures are frequently needed.

Plectin-1-targeted recognition for enhancing comprehensive therapy in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge due to its aggressive nature and poor prognosis. Gemcitabine (Gem), a primary therapeutic option, functions by inhibiting DNA synthesis and promoting apoptosis, thereby impeding the progression of PDAC. However, Gem is hindered by suboptimal pharmacokinetics and efficacy. In response to these challenges, we have developed a nanoparticle (NP) designed for specific recognition of plectin-1 in PDAC cell membranes. The NPs encapsulate Gem while demonstrating pH-responsive drug release characteristics in the acidic tumor microenvironment. This targeted approach enhances local drug delivery while alleviating concerns about systemic toxicity. Furthermore, the NPs are enriched with indocyanine green (ICG), renowned for its strong photothermal effects, thereby further enhancing therapeutic outcomes. This study presents an innovative therapeutic strategy for PDAC based on a plectin-1-targeted recognition delivery approach. The approach is applied to enhance chemotherapy, combined with photothermal therapy (PTT), inducing apoptosis in PDAC cell lines and improving the pharmacokinetics of Gem. In conclusion, the delivery strategy based on plectin-1-targeted recognition shows promising preclinical prospects for enhancing therapeutic efficacy in PDAC, offering valuable insights for future clinical applications.

Impact of CYP2D6 polymorphisms on the efficacy of tamoxifen in Iraqi women with breast cancer

Objectives: The aim of the present study was to investigate the impact of the CYP2D6 genetic polymorphism on clinical outcome in Iraqi breast cancer patients who were candidates for Tamoxifen therapy. Methods: Comprehensive CYP2D6 genotyping was performed in 140 Iraqi women with breast cancer who were women on adjuvant treatment with tamoxifen. Breast cancer patients recruited into the study were divided into two groups: seventy breast cancer women who had no history of recurrence at the time of sampling and had a long time on tamoxifen without recurrence and seventy breast cancer women who had recurrence at the time of sampling after one year of treatment with tamoxifen therapy. Recurrence free survival (RFS) was determined in the recruited patients. Results: Multiple genetic variants of the gene encoding the CYP2D6 enzyme were detected with significant differences in their frequencies and percentages in both recurrent and non-recurrent groups of breast cancer patients. The findings of this study suggest that interindividual variation in clinical outcome may be related to genetic variation in CYP2D6 enzyme, which is characterized by variable RFS periods. Conclusions: This study revealed that the CYP2D6 enzyme of breast cancer patients who participated in this study is highly polymorphic. The CYP2D6 gene of study participants exhibited different allelic combinations with variable frequencies. The multiple genetic variants (alleles) of the gene encoding the CYP2D6 enzyme exhibited significant differences in their frequencies and percentages in both recurrent and non-recurrent groups of breast cancer patients. .The study revealed variable Recurrence free survival (RFS) with highly polymorphic gene. Our study quotes the presence of increased CYP2D6 enzyme polymorphism is associated with variable clinical response.

Prosedur Percutaneous Trans Luminal Angioplasty (PTA) Pada Pasien Dengan Kasus Aneurisma Artery Popliteal (AAP)

Popliteal Artery Aneurysm (AAP) is a pathological dilation of the popliteal artery, and although often asymptomatic, can lead to serious complications such as rupture, thrombosis, or embolism. Aneurysms if ruptured can result in internal bleeding such as, stroke, and can sometimes be fatal. This research method is a literature review study, where literature exploration is carried out in various databases with keywords such as Percutaneous Transluminal Angioplasty (PTA)", Popliteal Artery Aneurysm (AAP) cases. Percutaneous transluminal angioplasty (PTA) in popliteal artery aneurysm (AAP) involves patient preparation, tools, procedure, post-operative care, and outcome evaluation. Patient preparation includes education, renal function evaluation, medication adjustment. Equipment preparation includes catheterization table, fluoroscopy system, various types of catheters, appropriate contrast agent. The PTA process includes insertion of the catheter into the femoral artery, evaluation and delineation of the popliteal artery, and completion of the procedure. PTA examination in AAP requires careful preparation and coordinated medical team collaboration to achieve optimal results. Percutaneous transluminal angioplasty (PTA) has proven to be effective as a primary therapeutic option to treat popliteal artery aneurysms (AAP) and prevent popliteal artery stenosis. Risk factors such as advanced age, male gender, and cardiovascular disease were considered in the literature analysis. Although PTA successfully improves the diameter of the popliteal artery as a minimally invasive method, it is important to recognize that the success of the procedure and the decision to use stents have a significant impact on the final outcome.

Patient reported long-term side effects on bowel function and anal pain in anal cancer survivors - 3- and 6-year results from the Swedish national ANCA study.

The primary therapeutic option for anal cancer treatment is chemoradiotherapy resulting in 80% survival. The aim of this study was to assess long-term bowel function impairment and anal pain at 3 and 6 years after anal cancer diagnosis, based on a hypothesis of an increase in impairment over time. A secondary aim was to investigate if chemoradiotherapy increased the risk for bowel impairment, compared to radiotherapy alone. The ANal CAncer study (ANCA) consists of a national Swedish cohort of patients diagnosed with anal cancer between 2011-2013. Patients within the study were invited to respond to a study-specific questionnaire at 3- and 6-years after diagnosis. Descriptive analyses for the primary endpoint and ordinal logistic regressions for secondary endpoint were performed. A total of 388 patients (84%) were included in the study. At 3 years of follow-up, 264 patients were alive. A total of 195 of these patients (74%) answered a study specific questionnaire, and at 6 years 154 patients (67%). Fifty-seven percent experienced bowel urgency at both 3 and 6 years. There was an increased risk for repeated bowel movement within 1 h (OR 2.44 [95% CI: 1.08-5.61, p = 0.03]) at 3 years in patients who had been treated by chemoradiation compared to radiotherapy alone. Impairment in bowel function and anal pain after anal cancer treatment should be expected and remains after 6 years. This suggests that long-term follow-up may be necessary in some form after customary follow-up. The addition of chemotherapy increases long-term side effects of bowel function.

Beyond Immunosuppression: The Intricate Relationship Between Tacrolimus and Microangiopathy.

Tacrolimus, widely known as Prograf, has become the preferred immunosuppressant for preventing graft rejection in solid organ transplant recipients, particularly in steroid-sparing regimens. Its efficacy and reduced risk of acute and chronic rejection compared to cyclosporine have made it the preferred treatment optionfor transplant patients. However, tacrolimus has drawbacks as it is associated with adverse effects, such as renal tubular necrosis, kidney failure, hypertension, metabolic acidosis, and new-onset diabetes mellitus. Among the less common but potentially severe complications is thrombotic microangiopathy linked to tacrolimus usage. Identifying and addressing this condition early on is crucial given its severity and potential complications. Manifestations of this microangiopathy can vary, encompassing renal, neurological, cardiac, and respiratory symptoms, and, in some cases, presenting as pancreatitis, intestinal ischemia, or skin abnormalities. Although conventional management often involves plasma exchange as the primary therapeutic option, recent insights into the pathophysiology have led to newer drugs, such as eculizumab and belatacept, offering promising outcomes. In this narrative review, we delve deeper into the underlying pathophysiological mechanisms of tacrolimus-induced thrombotic microangiopathy and aim to provide clinicians with valuable recommendations for efficient and timely treatment strategies. By understanding the complexities of this condition and staying abreast of the latest advancements in therapeutic options, healthcare providers can optimize patient outcomes and ensure safer tacrolimus administration in solid organ transplant recipients.

The glycopatterns of Pseudomonas aeruginosa as a potential biomarker for its carbapenem resistance.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections pose a significant challenge to effective treatment. Although carbapenems were once considered the primary therapeutic option for MDR P. aeruginosa, the clinical use of these antibiotics has become increasingly limited, and the exploration of alternative antimicrobial strategies remains necessary. Bacterial surface glycans are critical in response to antibiotics and represent an attractive therapeutic target. However, the understanding of the role of glycan structures in bacterial resistance is currently quite limited. In this study, we used lectin microarrays to analyze the differences in glycan alterations between 53 drug-sensitive P. aeruginosa (DSPA) strains and 57 carbapenem-resistant P. aeruginosa (CRPA) strains obtained from clinical isolates, with the goal of identifying important glycopatterns associated with carbapenem resistance. The results revealed significant differences in the expression levels of glycan structures [e.g., Fucα1-6GlcNAc, α-d-Man, and Fucα1-3(Galβ1-4)GlcNAc] recognized by 20 lectins (e.g., LCA, PSA, and AAL) on the bacterial surface. Furthermore, we applied K-fold cross-validation to determine the optimal parameters and constructed the DSPA and CRPA models using gradient boosting decision tree (GBDT) algorithm. The GBDT model presented the best performance in an independent test cohort, demonstrating that the screened glycopatterns could serve as potential biomarkers for differentiating bacterial resistance. Our study is the first to apply lectin microarrays to monitor carbapenem resistance in clinical P. aeruginosa isolates, and we hope that the methodology used in this work will serve as an important tool for exploring the association of bacterial resistance with glycosylation mechanisms.IMPORTANCEBacterial surface glycans are an attractive therapeutic target in response to antibiotics; however, current knowledge of the corresponding mechanisms is rather limited. Antimicrobial susceptibility testing, genome sequencing, and MALDI-TOF MS, commonly used in recent years to analyze bacterial resistance, are unable to rapidly and efficiently establish associations between glycans and resistance. The discovery of new antimicrobial strategies still requires the introduction of promising analytical methods. In this study, we applied lectin microarray technology and a machine-learning model to screen for important glycan structures associated with carbapenem-resistant P. aeruginosa. This work highlights that specific glycopatterns can be important biomarkers associated with bacterial antibiotic resistance, which promises to provide a rapid entry point for exploring new resistance mechanisms in pathogens.