Table of Contents
Advances in Liver Transplantation: Normothermic Machine Perfusion
Recent advances in liver transplantation have provided critical insights into the benefits of using normothermic machine perfusion (NMP) over static cold storage (SCS) for donation after circulatory death (DCD) recipients. In a retrospective single-center study, researchers compared 103 DCD liver transplant recipients receiving NMP-transported livers with 123 recipients of SCS-preserved livers. The study reported a significant reduction in post-reperfusion syndrome (PRS) rates in the NMP group (10.7% [95% CI, 5.5%–18.3%]) compared to the SCS group (42.3% [95% CI, 33.4%–51.5%]; p < .001). Additionally, differences were observed in the requirement of vasoactive medications during the reperfusion phase; specifically, elevated epinephrine and vasopressin bolus doses were required in the SCS group. The study also demonstrated reduced blood product utilization during both the post-reperfusion period and the initial 24-hour postoperative phase in the NMP group.
Key Variables and Findings
Below is a summary table highlighting selected intraoperative findings comparing NMP with SCS in DCD liver transplantation:
| Parameter | DCD-SCS Group | DCD-NMP Group | p-value |
|---|---|---|---|
| Post-Reperfusion Syndrome (%) | 42.3% | 10.7% | <.001 |
| Mean Epinephrine Bolus (µg) | 24.59 | 7.53 | <.001 |
| Mean Vasopressin Bolus (units) | 5.42 | 2.43 | <.001 |
| Post-Reperfusion RBC Utilization (units) | 5.29 | 3.69 | .006 |
| Anhepatic Phase RBC Utilization (units) | 2.89 | 1.99 | .04 |
| Actual Cold Ischemic Time (minutes) | 378.5 | 208.0 | <.001 |
The reduction in PRS is thought to be multifactorial. The NMP process maintains physiological conditions such as normothermia, which may moderate the release of inflammatory cytokines and reduce metabolic imbalances (e.g., reducing acidosis and hyperkalemia) on reperfusion. Moreover, improved lactate clearance and reduced cellular injury during NMP may contribute to these observed clinical benefits. With its potential to reduce both hemodynamic instability and transfusion requirements, NMP is emerging as a promising modality that could enhance outcomes in DCD liver transplantation.
Recognizing Drug-Induced Acute Pancreatitis: A Case Report
Acute pancreatitis (AP) is a serious inflammatory condition of the pancreas most commonly associated with gallstones and alcohol use. However, less frequent etiologies, such as drug-induced acute pancreatitis (DIAP), must also be considered in patients with recurrent episodes, particularly when the cause is not immediately identifiable. In one notable case report, a 58-year-old African-American female with a history of poorly controlled type 2 diabetes mellitus and chronic kidney disease presented with recurrent episodes of AP.
Case Overview
During her first hospitalization, the patient reported persistent epigastric pain following the consumption of a chili cheese dog, and computed tomography imaging confirmed acute interstitial pancreatitis with peripancreatic inflammatory stranding. Laboratory tests revealed markedly elevated serum lipase and triglyceride levels. Although hypertriglyceridemia was considered, the levels were below typical thresholds needed to trigger pancreatitis. Additionally, the patient’s medication history revealed use of hydrochlorothiazide (HCTZ), a drug known to have rare associations with DIAP.
Following the first episode, HCTZ was discontinued and appropriate alternative antihypertensive therapy was initiated. Despite initial improvement and resolution of inflammatory changes on imaging, the patient was rehospitalized 16 months later after inadvertently resuming HCTZ. Her laboratory findings during the second episode revealed elevated lipase, hypercalcemia, and electrolyte disturbances, which further supported HCTZ-induced pancreatic injury. The close temporal relationship between HCTZ use and the onset of AP episodes underscores the importance of thorough medication reconciliation in patients with recurrent pancreatitis.
Multiparametric Imaging in Breast Cancer: A Personalized Approach
Breast cancer diagnosis and management have significantly improved with the advent of multiparametric imaging techniques. Combining dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), and T2-weighted imaging provides a comprehensive assessment of tumor vascularity, cellular density, and peritumoral environment. This integrated modality enhances diagnostic accuracy, helps distinguish between benign and malignant lesions, and contributes to the prediction of tumor subtypes and treatment response.
Imaging Parameters and Clinical Significance
DCE-MRI is widely recognized as the cornerstone of breast imaging. It captures the kinetics of contrast enhancement and provides semiquantitative parameters such as maximum slope (MS), time to enhancement (TTE), and wash-in slope (WIS). DWI, on the other hand, offers quantitative insights through the apparent diffusion coefficient (ADC) and advanced measures such as diffusion kurtosis imaging (DKI). Together, these modalities not only support early detection of disease but also lay the groundwork for personalized therapy by correlating imaging features with molecular and genetic markers.
Below is an illustrative table summarizing key MRI parameters in breast cancer imaging:
| Imaging Modality | Key Parameters | Clinical Significance |
|---|---|---|
| DCE-MRI | MS, TTE, WIS | Reflects tumor vascularity and permeability |
| Diffusion-Weighted | ADC, DKI | Indicates tumor cellularity and microstructural changes |
| T2-Weighted Imaging | Signal intensity | Assesses peritumoral edema and tissue water content |
Multiparametric approaches enable clinicians to make more accurate diagnoses and to predict response to neoadjuvant chemotherapy. The integration of these imaging biomarkers is crucial in a personalized treatment strategy, as it allows for the tailoring of therapeutic interventions based on the unique characteristics of each breast tumor.
Incidental Findings in Appendectomy: The Role of Surgery
Acute appendicitis is one of the most common surgical emergencies and is typically managed by appendectomy. In many cases, the surgical specimen is sent for histopathological analysis, which can reveal incidental malignancies. One such instance is the discovery of an appendiceal neuroendocrine tumor (aNET) post-appendectomy.
Case Details and Clinical Implications
A 25-year-old female patient underwent laparoscopic appendectomy for presumed acute appendicitis. Unexpectedly, histopathological examination revealed a well-differentiated grade 1 aNET measuring 3.5 cm that had invaded the peri-appendiceal tissue. The discovery of the tumor necessitated further diagnostic workup, including colonoscopy and computed tomography imaging, leading to a subsequent right hemicolectomy to ensure complete tumor resection.
This case highlights the diagnostic advantage of surgical intervention in the management of appendicitis. Although non-surgical management has been proposed for uncomplicated cases, an appendectomy allows for definitive treatment and offers the opportunity for histological evaluation to detect incidental pathologies that may significantly affect long-term survival and management.
Diabetes Cascade of Care in HIV-Positive Populations
The prevalence of diabetes has been increasing worldwide, and among people living with HIV, diabetes poses a significant comorbidity that can complicate clinical outcomes. A study conducted in a tertiary care center in Mexico City examined the diabetes cascade of care (DMC) in HIV-positive patients, focusing on screening, diagnosis, treatment, and goal attainment for blood pressure, glycemic control, and lipid parameters (the “ABC” goals).
Key Findings
- Prevalence: The study reported that 6.4% of active HIV-positive patients had diabetes, while 9.4% had pre-diabetes.
- Medication Use: About 74.4% of patients with diabetes were receiving glycemic control medications; however, only 26.2% achieved an HbA1c below 7%.
- Hypertension and Dyslipidemia: All diabetic patients with hypertension (31.7%) were on blood pressure medications, yet only 55.3% of those with dyslipidemia were controlled with LDL levels below 100 mg/dL.
- Overall ABC Goals Attainment: Merely 25.6% of patients with complete data achieved all the ABC goals, highlighting a significant gap in integrated diabetes care among HIV-infected individuals.
Below is a summary table based on key metrics from the study:
| Parameter | Diabetes Patients (%) | Control/Goal Attainment (%) |
|---|---|---|
| Diabetes Prevalence | 6.4 | N/A |
| Pre-Diabetes Prevalence | 9.4 | N/A |
| On Glycemic Medications | 74.4 | 26.2 (HbA1c < 7%) |
| Hypertension (controlled) | 31.7 (all treated) | 100 (BP < 140/90 mmHg) |
| Dyslipidemia (on medication) | 77.4 | 58.6 (LDL < 100 mg/dL) |
| Attainment of full ABC Goals | N/A | 25.6 |
This cascade of care study underscores the urgent need to improve chronic disease management in HIV-positive populations through a multidisciplinary approach integrating infectious disease specialists and primary care providers.
Inflammatory Biomarkers in Preeclampsia: Ischemia Modified Albumin
Preeclampsia is a hypertensive disorder of pregnancy that significantly contributes to maternal and perinatal morbidity. The identification of reliable biomarkers to predict and monitor preeclampsia is of paramount importance. One promising biomarker is ischemia modified albumin (IMA).
Study Insights
A prospective case-control study compared serum IMA levels between preeclamptic and healthy pregnant women. The study demonstrated that mean IMA levels were significantly higher in the preeclampsia group (mean IMA ≈1.02 ABSU) compared to healthy controls (mean IMA ≈0.93 ABSU; p < 0.001). Although IMA levels could distinguish between preeclamptic and healthy pregnancies, they were not correlated with preeclampsia severity. Receiver Operating Characteristic (ROC) curve analysis identified an optimal IMA cut-off value of >0.98 ABSU, with moderate sensitivity (65.15%) and specificity (64.71%) for predicting preeclampsia.
The findings indicate that while IMA has potential as an early marker for preeclampsia, its role in determining severity is limited. Continuous monitoring and the incorporation of additional biomarkers might further enhance clinical prediction accuracy.
The Role of C-Reactive Protein in Chronic Pain
Chronic pain remains a major public health concern, affecting millions of adults and leading to significant economic and personal burdens. Inflammation is increasingly recognized as a contributor to chronic pain. C-reactive protein (CRP), a marker of systemic inflammation produced by the liver, has been studied extensively in this context.
Study Overview
A nationwide cross-sectional study using NHANES data evaluated the association between CRP levels and chronic pain in US adults. The study stratified patients into quartiles based on their CRP levels. It was observed that individuals in the highest CRP quartile (≥0.52 mg/dL) had a significantly higher incidence of chronic pain compared to those in the lowest quartile (<0.09 mg/dL). Multivariate logistic regression demonstrated a dose-response relationship, even after adjusting for confounders such as age, gender, smoking status, and comorbidities. The study provided evidence that systemic inflammation, as measured by CRP, may play a role in chronic pain syndromes and suggests that anti-inflammatory strategies may improve pain management.
Data Summary
| CRP Quartile (mg/dL) | Incidence of Chronic Pain (%) |
|---|---|
| < 0.09 | 22.9 |
| 0.09 – 0.23 | 25.9 |
| 0.23 – 0.52 | 24.9 |
| ≥ 0.52 | 26.2 |
These findings support further investigation into therapeutic interventions aimed at reducing systemic inflammation as a means of alleviating chronic pain.
Genetic Insights: Shared Etiology in GERD and COPD
COPD and GERD are two common conditions that frequently coexist and exacerbate each other. Recent whole-genome sequencing studies have begun to unravel the complex genetic architecture underlying these comorbidities. In a large genetic study involving over 12,000 participants from multiple cohorts, researchers estimated the narrow-sense heritability of co-morbid GERD and COPD in non-Hispanic White participants to be approximately 39.7%. In contrast, the heritability of COPD alone was estimated at 28.3% in this group, while in African American participants, COPD heritability was significantly higher at 66.2%.
Highlights from the Genetic Analysis
- Shared Heritability: The high co-heritability suggests that a substantial portion of the genetic risk for GERD in patients with COPD may be driven by pleiotropic variants affecting both diseases.
- Key Loci: Several independent loci were identified as being suggestively associated with the comorbid phenotype, including loci in or near the genes LINC02493, FRYL, and DPYD. Fine-mapping highlighted the potential causal role of these variants.
- Pathway Enrichment: Gene-set enrichment analyses confirmed that implicated loci were enriched in pathways related to oxidative stress, G protein-coupled receptor (GPCR) signaling, and IL6/STAT3 signaling—mechanisms important in both GERD and COPD pathogenesis.
Below is an abbreviated data table from the study summarizing heritability estimates:
| Phenotype | Ancestry Group | Heritability (h², %) | 95% Confidence Interval |
|---|---|---|---|
| Co-morbid GERD and COPD | Non-Hispanic White (NHW) | 39.7 | 32.2–47.0 |
| COPD Only (NHW) | Non-Hispanic White (NHW) | 28.3 | 23.5–33.1 |
| COPD Only (African American) | African American (AA) | 66.2 | 54.3–78.0 |
| GERD Only (NHW) | Non-Hispanic White (NHW) | Not significant (–0.01) | –0.08 to 0.06 |
These genetic discoveries offer a window into the shared biological pathways and provide potential targets for novel therapeutic strategies particularly aimed at mitigating GERD-related exacerbation of COPD.
Frequently Asked Questions (FAQ)
What is normothermic machine perfusion (NMP) and why is it beneficial in liver transplantation?
NMP is a technique used to preserve donor organs at near-physiologic temperatures while sustaining metabolic activity. It reduces ischemia-reperfusion injury, improves lactate clearance, and decreases the need for vasoactive medications compared to traditional static cold storage. This leads to lower rates of post-reperfusion syndrome and reduced blood product utilization, ultimately improving transplant outcomes.
How can hydrochlorothiazide (HCTZ) cause acute pancreatitis?
Although rare, HCTZ-induced pancreatitis is thought to occur via mechanisms such as direct toxicity to pancreatic acinar cells, disturbances in fluid and electrolyte homeostasis, and the induction of hypercalcemiRecognizing HCTZ as a potential trigger is crucial when evaluating patients with recurrent pancreatitis of unclear etiology.
What does multiparametric breast imaging involve?
Multiparametric breast imaging integrates various MRI techniques—such as DCE-MRI, diffusion-weighted imaging, and T2-weighted imaging—to assess tumor vascularity, cellular density, and the surrounding tissue environment. This approach improves diagnostic accuracy and helps predict tumor subtypes and treatment responses, thereby supporting personalized breast cancer therapy.
Why is surgical appendectomy still important in the era of non-surgical management of appendicitis?
While non-surgical management can be effective in uncomplicated cases, surgical appendectomy provides tissue for histopathological analysis, which can uncover incidental findings such as neuroendocrine tumors. Early detection of such malignancies can significantly alter patient management and improve prognosis.
What are the “ABC” goals in diabetes care and why are they particularly important for HIV-positive patients?
The “ABC” goals in diabetes care refer to controlling A1c (glycemic control), Blood pressure, and Cholesterol (LDL levels). For HIV-positive patients, who have a higher prevalence of metabolic complications, meeting these targets is essential to prevent cardiovascular diseases and other comorbidities. However, studies indicate that many patients do not achieve these comprehensive targets, underscoring the need for integrated care strategies.
Can ischemia modified albumin (IMA) be used as a definitive diagnostic marker for preeclampsia?
IMA levels are significantly elevated in preeclamptic pregnancies compared to healthy ones. However, while IMA can aid in early recognition of preeclampsia, its levels are not well correlated with disease severity. Thus, it should be used in conjunction with other clinical markers rather than as a stand-alone diagnostic test.
What is the significance of CRP in chronic pain management?
Elevated CRP is indicative of systemic inflammation, which has been associated with an increased risk of chronic pain. Studies suggest that higher CRP levels correlate with a greater incidence of chronic pain, and this association underscores the potential of anti-inflammatory interventions in improving pain management strategies.
How do genetic studies help in understanding common comorbidities like GERD and COPD?
Genetic studies, particularly those using whole-genome sequencing, allow researchers to estimate heritability and identify shared genetic loci between conditions such as GERD and COPD. These findings support the idea of common biological pathways—such as those involved in oxidative stress and GPCR signaling—which can become targets for novel therapeutic interventions to manage both conditions simultaneously.
References
- Donation After Circulatory Death Liver Transplantation: Impact of Normothermic Machine Perfusion on Key Variables. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11805485/
- Recurrent Acute Pancreatitis Associated With Hydrochlorothiazide Use: A Case Report. Retrieved from https://doi.org/10.7759/cureus.77108
- Multiparametric Approach to Breast Cancer With Emphasis on Magnetic Resonance Imaging in the Era of Personalized Breast Cancer Treatment. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11805492/
- Incidental Appendiceal Neuroendocrine Tumor Post Appendectomy: Surgery Is Here to Stay. Retrieved from https://doi.org/10.7759/cureus.78700
- A cascade of care for diabetes in people living with HIV in a tertiary care center in Mexico City. Retrieved from https://pubmed.ncbi.nlm.nih.gov/11805464/
- Comparison of serum ischemia modified albumin levels between preeclamptic and healthy pregnant women. Retrieved from https://doi.org/10.61622/rbgo/2024rbgo97
- Association between C-reactive protein and chronic pain in US adults: A nationwide cross-sectional study. Retrieved from https://doi.org/10.1371/journal.pone.0315602
- Novel risk loci encompassing genes influencing STAT3, GPCR, and oxidative stress signaling are associated with co-morbid GERD and COPD. Retrieved from https://doi.org/10.1371/journal.pgen.1011531