The performance of bronchoalveolar lavage Aspergillus PCR testing in solid organ transplant recipients with invasive pulmonary aspergillosis.

BACKGROUND: Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients. METHODS: We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria. RESULTS: Ninety-nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non-Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty-four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%-93%), and the specificity was 98% (95% CI 93%-99%). CONCLUSION: BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test.

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.

Photosynthetic activity and metabolic profiling of bread wheat cultivars contrasting in drought tolerance.

The rapid increase in population growth under changing climatic conditions causes drought stress, threatening world food security. The identification of physiological and biochemical traits acting as yield-limiting factors in diverse germplasm is pre-requisite for genetic improvement under water-deficit conditions. The major aim of the present study was the identification of drought-tolerant wheat cultivars with a novel source of drought tolerance from local wheat germplasm. The study was conducted to screen 40 local wheat cultivars against drought stress at different growth stages. Barani-83, Blue Silver, Pak-81, and Pasban-90 containing shoot and root fresh weight >60% of control and shoot and root dry weight >80% and 70% of control, respectively, P (% of control >80 in shoot and >88 in root), K+ (>85% of control), and quantum yield of PSII > 90% of control under polyethylene glycol (PEG)-induced drought stress at seedling stage can be considered as tolerant, while more reduction in these parameters make FSD-08, Lasani-08, Punjab-96, and Sahar-06 as drought-sensitive cultivars. FSD-08 and Lasani-08 could not maintain growth and yield due to protoplasmic dehydration, decreased turgidity, cell enlargement, and cell division due to drought treatment at adult growth stage. Stability of leaf chlorophyll content (<20% decrease) reflects photosynthetic efficiency of tolerant cultivars, while ~30 µmol/g fwt concentration of proline, 100%-200% increase in free amino acids, and ~50% increase in accumulation of soluble sugars were associated with maintaining leaf water status by osmotic adjustment. Raw OJIP chlorophyll fluorescence curves revealed a decrease in fluorescence at O, J, I, and P steps in sensitive genotypes FSD-08 and Lasani-08, showing greater damage to photosynthetic machinery and greater decrease in JIP test parameters, performance index (PIABS), maximum quantum yield (Fv/Fm) associated with increase in Vj, absorption (ABS/RC), and dissipation per reaction center (DIo/RC) while a decrease in electron transport per reaction center (ETo/RC). During the present study, differential modifications in morpho-physiological, biochemical, and photosynthetic attributes that alleviate the damaging effects of drought stress in locally grown wheat cultivars were analyzed. Selected tolerant cultivars could be explored in various breeding programs to produce new wheat genotypes with adaptive traits to withstand water stress.

Association of nonalcoholic fatty liver disease with acute cholangitis: a nationwide propensity-matched analysis from the United States.

Background: Nonalcoholic fatty liver disease (NAFLD) has previously been linked to several disease states with an impact on patient outcomes. However, clinical evidence on the association between NAFLD and acute cholangitis (AC) remains scarce. We aimed to evaluate the potential association between NAFLD and AC. Methods: We conducted a retrospective cohort study using the US National Inpatient Sample database from 2016 to 2019 to analyze primary AC hospitalizations with NAFLD compared to non-NAFLD in a 1:1 propensity-matched population. Results: A total of 1550 AC patients with NAFLD were matched to 1550 AC patients without NAFLD. NAFLD had a higher association with AC when compared to patients without NAFLD, with an odds ratio of 2.33 (95% CI [1.81-3.0], P < 0.001). The length of stay was higher in NAFLD than in non-NAFLD (4 vs 3 days, P < 0.001). The median inpatient charges in NAFLD were also higher than in the non-NAFLD cohort ($36,182 vs $35,244, P < 0.001). Inpatient mortality was higher in NAFLD compared to non-NAFLD (1.6% vs 0%, P < 0.001). There was an increased prevalence of portal vein thrombosis (3.2% vs 0%), acute kidney injury (24.2% vs 17.7%), sepsis (3.2% vs 1.6%), mechanical ventilation (3.2% vs 0%), and percutaneous cholecystostomy tube insertion (3.2% vs 1.6%) in NAFLD compared to non-NAFLD (P < 0.05). NAFLD also had a higher association with acute cholecystitis, with an odds ratio of 3.70 (95% CI [3.19-4.29], P < 0.001). Conclusions: This study showed an association between NALFD and AC, resulting in increased length of stay, hospital charges, and inpatient mortality. Underlying NAFLD also increases acute complications of AC.

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.

Co3 Se4 Quantum Dots as an Ultrastable Host Material for Potassium-Ion Intercalation.

Potassium-ion batteries (KIBs) are receiving increased attention due to their cost-effective and similar energy-storage mechanism to lithium-ion batteries. However, the lack of appropriate electrode materials is still hampered for their development, which is mainly caused by the large size of the potassium ions (1.38 Å) including low structural stability and poor electrochemical redox reaction kinetics. Herein, Co3 Se4 quantum dots (QD) encapsulated by N-doped carbon (CSC) are reported as an anode material for KIBs, in which a morphology change process occurs. Benefiting from the unique uniform nanostructure reducing the ion-diffusion length, the improved electronic conductivity, and the enhanced protective effect of N-doped carbon (NC) alleviating volume fluctuation, the CSC demonstrates excellent electrochemical performance. The core-shell-like CSC composite demonstrates remarkable discharge capacity (410 mA h g-1 at 0.1 A g-1 after 550 cycles, 360 mA h g-1 at 0.5 A g-1 after 3200 cycles) and excellent cyclic performance over 10 000 cycles at 1 A g-1 . Density functional theory calculations show a larger reaction energy of Co3 Se4 QD than bulk Co3 Se4 , a lower barrier of K atom migration in Co3 Se4 QD than bulk Co3 Se4 , and also favor the intercalation reaction rather than replacement reaction. In situ X-ray diffraction and ex situ transmission electron microscopy are further used to evaluate potassiation/depotassiation phenomena.

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.

Identification of novel source of salt tolerance in local bread wheat germplasm using morpho-physiological and biochemical attributes.

Salt tolerant wheat cultivars may be used as genetic resource for wheat breeding to ensure yield stability in future. The study was aimed to select salt tolerant cultivar(s) to identify novel source of salt tolerance in local wheat germplasm. Initially, 40 local wheat cultivars were screened at 150 mM NaCl stress at seedling stage. Selected salt-tolerant (three; S-24, LU-26S and Pasban-90) and salt-sensitive (four; MH-97, Kohistan-97, Inqilab-91 and Iqbal-2000) wheat cultivars were further evaluated using growth, yield, biochemical and physiological attributes. Growth and yield of selected cultivars were reduced under salt stress due to decline in plant water status, limited uptake of macronutrients (N, P and K), reduced K+/Na+ ratio, photosynthetic pigments and quantum yield of PSII. Wheat plants tried to acclimate salt stress by osmotic adjustment (accumulation of total soluble sugars, proline and free amino acids). Degree of salinity tolerance in cvs. S-24 and LU-26S found to be associated with maintenance of K+/Na+ ratio, osmo-protectant and photosynthetic activity and can be used as donor for salt tolerance in wheat breeding program at least in Pakistan. These cultivars can be further characterized using molecular techniques to identify QTLs/genes for salt exclusion, osmo-protectant and photosynthetic activity for molecular breeding.

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.

Cardiovascular Autonomic Neuropathy and its Association with Cardiovascular and All-cause Mortality in Patients with End-stage Renal Disease.

Background End-stage renal disease frequently leads to increased cardiovascular mortality. Cardiovascular autonomic neuropathy (CAN) may be predictive of cardiac arrhythmias and sudden cardiac death in patients with end-stage renal disease. Methods A total of 70 patients with end-stage renal disease were included in the study. The assessment of cardiac dysautonomia was based on the four standardized tests performed at the baseline and, again, at the end of the study. The criteria for CAN included at least two abnormal test results. Results Fifty of 70 patients completed the study and were followed-up after one year. Out of the 50 patients, 44 (88%) had CAN at baseline. Twelve (24%) patients died at the one-year follow-up. Sudden cardiac death was reported in seven out of 12 (58%) patients. All seven patients who died had high dysautonomia scores (three abnormal tests) at the baseline. There was a significantly higher percentage of patients with all four abnormal tests amongst patients who died of any cause (56% vs. 17%; RR 6.07, 95% CI 1.29-28.49; p-value 0.02) or due to sudden cardiac death (43% vs. 10.5%; RR 6.37, 95% CI 1.03-39.36; p-value 0.04). All five patients who did not have CAN at the baseline developed this abnormality on repeat testing after one year. Conclusion The prevalence of CAN in patients with end-stage renal disease on maintenance hemodialysis was significantly higher. CAN was an independent predictor of all-cause and cardiovascular mortality, which highlights it as a risk stratification tool in patients with end-stage renal disease.

Neuroendocrine responses to a cold pressor stimulus in polydipsic hyponatremic and in matched schizophrenic patients.

Schizophrenia, many believe, reflects an enhanced vulnerability to psychological stress. Controlled exposure to stressors, however, has produced inconclusive results, particularly with regards to neurohormones. Some of the variability may be attributable to the nature and psychological significance of the stimulus and failure to control physiologic confounds. In addition, it is possible that the heterogeneity of schizophrenia is an important factor. In a carefully designed study and in a controlled setting, we measured the neuroendocrine response of eight polydipsic hyponatremic (PHS), seven polydipsic normonatremic (PNS), and nine nonpolydipsic normonatremic (NNS) (ie normal water balance) schizophrenic in-patients as well as 12 healthy controls (HC) to two different stressors: one of which appears to influence neuroendocrine secretion through its psychological (cold pressor) and the other (upright posture) through its systemic actions. Subjects in the three psychiatric groups were stabilized and acclimated to the research setting, and all received saline to normalize plasma osmolality. Following the cold pressor, plasma adrenocorticotropin and cortisol levels showed a more prolonged rise in PHS patients relative to PNS patients. NNS patients, in contrast, exhibited blunted responses relative to both of the polydipsic groups and the HC. Peak vasopressin responses were also greater in PHS and blunted in NNS patients. Responses to the postural stimulus were similar across patient groups. These findings provide a mechanism for life threatening water intoxication in schizophrenia; help to reconcile conflicting findings of stress responsiveness in schizophrenia; and potentially identify a discrete patient subset with enhanced vulnerability to psychological stress.

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.

Principles of endosonography and imaging.

Accurate interpretation of ultrasound images requires knowledge of the principles of ultrasound and how it interacts with tissue. This article outlines the important principles that every endosonographer should know and provides clinical implications to make the material relevant to endosonographers.

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.

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.

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.