Acute pancreatitis secondary to tamoxifen-associated hypertriglyceridemia: A clinical update.

INTRODUCTION: Drug-induced pancreatitis has been increasingly recognized, but it is frequently encountered as an inconspicuous etiology. The underlying mechanisms of injury vary with different drugs. Tamoxifen is a frequently used anticancer drug that acts by selective modulation of the estrogen receptor in patients with breast cancer. Tamoxifen-induced hypertriglyceridemia is a relatively rare etiological factor for acute pancreatitis. However, acute pancreatitis secondary to this adverse effect remains an exceedingly important clinicopathologic entity. CASE REPORT: We hereby delineate a rare case of acute pancreatitis secondary to hypertriglyceridemia in a patient who was on tamoxifen treatment for the past 3 years. Her serum lipase and triglyceride levels were markedly elevated at 14,285 IU/L and 20,344 mg/dL, respectively. The diagnosis was considered based on the findings of a standard diagnostic workup and exclusion of alternative causes of acute pancreatitis. MANAGEMENT AND OUTCOME: The patient was instituted prompt treatment with intravenous insulin infusion and gemfibrozil. The clinical outcome was favorable with no complications. Tamoxifen was permanently discontinued and was replaced with letrozole. DISCUSSION: This article illustrates that acute pancreatitis should be considered in the differential diagnoses of abdominal pain and elevated pancreatic enzymes in patients undergoing tamoxifen treatment. It also underscores the importance of pre- and post-tamoxifen lipid screening, especially in patients with a history of dyslipidemia and diabetes mellitus. It will facilitate an expedient detection of hypertriglyceridemia, potentially saving patients from associated morbidity and mortality.

Role of mineral nutrients, antioxidants, osmotic adjustment and PSII stability in salt tolerance of contrasting wheat genotypes.

Global food production is threatened due to increasing salinity and can be stabilized by improving salt tolerance of crops. In the current study, salt tolerance potential of 40 local wheat cultivars against 150 mM NaCl stress was explored. Salt treatment at seedling stage caused less reduction in biomass, K+ and P while more decline of Na+ in tolerant cultivars due to reduced translocation and enhanced exclusion of Na+ from leaves. Principal component analysis based selected S-24, LU-26S, Pasban-90 (salt tolerant) and MH-97, Kohistan-97, Inqilab-91 and Iqbal-2000 (salt sensitive) cultivars were evaluated at adult stage applying 150 mM salinity. Osmotic adjustment by accumulation of soluble sugars and proline and accelerated antioxidant enzymes activities caused efficient scavenging of reactive oxygen species making S-24 and LU-26S tolerant while in MH-97 and Kohistan-97, high MDA represent greater membrane damage due to oxidative stress making them salt sensitive. Chlorophyll a fluorescence transients confirmed better efficiency of photosystem II in S-24 and LU-26S based on energy fluxes (ABS/RC, TRo/RC, ETo/RC and DIo/RC), performance index (PIABS) and maximum quantum yield (Fv/Fm). These findings can be correlated using molecular techniques to identify genes for salt exclusion, osmotic adjustment and photosynthetic activity for use in molecular breeding programs.

Simultaneous Left Ventricular Aneurysm and Ventricular Septal Rupture Complicating Delayed STEMI Presentation: A Case-Based Review of Post-MI Mechanical Complications Amid the COVID-19 Pandemic.

Amid the coronavirus disease 2019 (COVID-19) pandemic, there is an unprecedented increase in public avoidance of hospitals predominantly driven by fear of contracting the virus. Recent publications highlight a re-emergence of rare post-myocardial infarction complications. While mechanical complications are infrequent in the era of primary percutaneous coronary intervention, they are associated with high mortality rates. The concurrent occurrence of mechanical complications such as left ventricular aneurysm and ventricular septal rupture is an extremely rare entity. We hereby delineate a unique case of a 53-year-old Caucasian male who underwent successful concomitant closure of a ventricular septal rupture, left ventricular aneurysmectomy, and 3-vessel coronary artery bypass grafting. Due to a delayed initial presentation owing to the patient's fear of contracting COVID-19, the surgery was carried out 3 months after the myocardial infarction. His postoperative evaluation confirmed normal contractility of the left ventricle and complete closure of the ventricular septal rupture. Six months postoperatively, the patient continues to do well. We also present a literature review of the mechanical complications following delayed presentation of myocardial infarction amid the COVID-19 pandemic. This article illustrates that clinicians should remain cognizant of these extremely rare but potentially lethal collateral effects during the ongoing global public-health challenge. Furthermore, it highlights a significant concern regarding the delay in first medical contact due to the reluctance of patients to visit the hospital during the COVID-19 pandemic.

Hepatic involvement and portal hypertension predict mortality in chronic granulomatous disease.

BACKGROUND & AIMS: Chronic granulomatous disease (CGD) is a rare genetic disorder, predisposing affected individuals to recurrent infectious complications and shortened survival. Liver involvement in CGD includes vascular abnormalities, which may lead to noncirrhotic portal hypertension. METHODS: To evaluate the impact of noncirrhotic portal hypertension on survival in CGD, all records from 194 patients followed up at the National Institutes of Health with CGD were reviewed. Cox proportional hazards regression was used to determine factors associated with mortality. RESULTS: Twenty-four patients died, all from infectious complications. By Cox regression, factors associated with mortality were as follows: (1) decreases in platelet count (>9000/microL/y; hazard ratio, 4.7; P = .007), (2) alkaline phosphatase level increases (>0.25/y; hazard ratio, 4.5; P = .01) and (3) history of liver abscess (hazard ratio, 3.1; P = .03). By regression analysis, decreasing platelet count was associated with increasing portal vein diameter, splenomegaly, increased serum immunoglobulin G level, and increasing number of alanine aminotransferase increases; greater number of alkaline phosphatase level increases and abscess were both associated with increasing age and number of infections. Prospective evaluation revealed increased hepatic-venous pressure gradients in 2 patients with progressive thrombocytopenia, suggestive of portal hypertension. CONCLUSIONS: These data suggest mortality in patients with CGD is associated with the development of noncirrhotic portal hypertension, likely owing to injury to the microvasculature of the liver from repeated systemic and hepatic infections. The slope of decline in platelet count may be a useful measure of progression of portal hypertension over time. Furthermore, the data illustrate the potential independent effect of portal hypertension on clinical outcome outside the setting of cirrhosis.

Hepatic abnormalities in patients with chronic granulomatous disease.

UNLABELLED: Chronic granulomatous disease (CGD) is a rare congenital disorder characterized by repeated bacterial and fungal infections. Aside from a high incidence of liver abscess, little is known about hepatic involvement in CGD. The aim of this study was to describe the spectrum of liver abnormalities seen in CGD. The charts of 194 patients with CGD followed at the NIH were reviewed, with a focus on liver abnormalities. Liver enzyme elevations occurred on at least one occasion in 73% of patients during a mean of 8.9 years of follow-up. ALT elevations were generally transient. Although transient alkaline phosphatase (ALP) elevations were also common, persistent ALP elevations lasting up to 17.6 years were seen in 25% of patients. Liver abscess occurred in 35% of patients. Drug-induced hepatotoxicity was documented in 15% of patients but likely occurred more frequently. Hepatomegaly was found in 34% and splenomegaly in 56% of patients. Liver histology showed granulomata in 75% and lobular hepatitis in 90% of specimens. Venopathy of the portal vein was common (80%) and associated with splenomegaly. Venopathy of the central vein was also common (63%) and was associated with the number of abscess episodes. Nodular regenerative hyperplasia (NRH) was seen in 9 patients, including 6 of 12 autopsy specimens. CONCLUSION: Liver enzyme abnormalities occur frequently in patients with CGD. In addition to liver abscesses and granulomata, drug hepatotoxicity is likely underappreciated. Vascular lesions such as venopathy and--to a lesser extent--NRH are common. The cause and clinical consequences of venopathy await prospective evaluation.

CT and MRI of hepatic abscess in patients with chronic granulomatous disease.

OBJECTIVE: We describe the spectrum of radiologic appearances of hepatic abscesses in patients with chronic granulomatous disease (CGD), a hereditary immunodeficiency presenting in childhood that occurs at a rate of 1 in 200,000-250,000 live births and predisposes patients to infection with catalase-positive organisms. CONCLUSION: Hepatic abscesses in patients with CGD show an atypical radiologic appearance compared with sporadic hepatic abscesses, and they are characterized by homogeneous enhancement and multiseptal enhancement. In the appropriate clinical setting, the appearance of an enhancing mass should suggest the possibility of a CGD-related hepatic abscess.

Nodular regenerative hyperplasia and severe portal hypertension in cystinosis.

BACKGROUND & AIMS: Cystinosis is a rare autosomal-recessive disorder characterized by the intralysosomal accumulation of cystine, which is responsible for widespread tissue destruction. Liver biopsy specimens of patients with cystinosis show cystine crystal formation in Kupffer cells. However, significant liver disease and portal hypertension is not a common complication of cystinosis. We report the case histories of 2 young men with poorly treated nephropathic cystinosis who developed noncirrhotic portal hypertension with evidence of nodular regenerative hyperplasia (NRH). METHODS: Liver biopsy examinations, upper and lower endoscopy with biopsy examination, imaging studies, venous pressure measurements, and laboratory investigations were used to evaluate the causes of the liver disease and portal hypertension. RESULTS: Histologic examination of liver biopsy specimens from both patients showed changes characteristic of NRH with portal hypertension documented by measurement of pressure gradients. In addition, endoscopy in the first patient showed varices and portal hypertensive gastropathy. CONCLUSIONS: NRH was confirmed by histologic examination of the liver in both patients and is the likely cause of their portal hypertension. NRH may represent a rare, late complication of cystinosis, although the mechanism remains undefined.

Intestinal disease in Hermansky-Pudlak syndrome: occurrence of colitis and relation to genotype.

BACKGROUND & AIMS: Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction, results from mutations in 1 of at least 7 different genes. Some patients develop a fatal pulmonary fibrosis and others a disabling colitis. This study aimed to document the occurrence of colitis among HPS patients, characterize gastrointestinal tract involvement in HPS, and analyze the distribution of colitis among HPS genotypes. METHODS: Of the 122 HPS patients followed at the National Institutes of Health Clinical Center between 1993 and 2005, 24 were evaluated by endoscopy for gastrointestinal complaints. The histology of gastrointestinal biopsies was retrospectively examined to assess for inflammatory changes, granulomata, and pigmented macrophages. These data were compared with symptoms and HPS genetic subtypes. RESULTS: At colonoscopy, 7 of 23 patients (30%) had endoscopic mucosal abnormalities, including nodularity, erythema, petechiae, or erosions. Six of these 7 patients (86%) had findings of colitis on biopsy. Of the 16 patients with normal-appearing colonic mucosa, 2 patients (12%) had colitis on biopsy. Pigmented macrophages were also observed in the colonic lamina propria in 16 of the 23 patients (70%). Of the 8 patients with confirmed colitis, 7 had the HPS-1 subtype, and 1 had the HPS-4 subtype. CONCLUSIONS: There is an increased frequency of colitis in our population of 122 HPS patients (8/122, 7%) and in HPS patients referred specifically for symptom evaluation (8/24, 33%). Colitis was found in patients with HPS-1 and HPS-4 genotypes.