How does long-term parenteral nutrition impact the bone mineral status of children with intestinal failure?

Patients on long-term parenteral nutrition (PN) are at significantly increased risk for the development of metabolic bone disease (MBD); this condition is characterized by incomplete mineralization of osteoid with consequent disturbances ranging from osteopenia to severe bone disease with fractures. The aim of the study was: (1) to evaluate the prevalence of MBD, (2) to identify the PN- or intestinal failure (IF)-related factors and (3) to assess annual changes of bone mineral status. Since September 2005 all patients affected by IF and treated with PN started a BMD evaluation program using dual-energy X-ray absorptiometry (DXA). Twenty-four IF patients were included [15 with short bowel syndrome (SBS), 5 with severe protracted diarrhea and 4 with chronic intestinal pseudostruction]. The bone mineral density (BMD) Z-score was significantly lower in patients than in the control group. In our series SBS patients showed a BMD Z-score significantly higher in comparison with the medical causes of IF. No significant correlations were found between bone mineral status and PN duration and nutrient intake. Nine IF patients were submitted to a second DXA evaluation after 1 year from the baseline. All bone mineral variables were significantly increased at the second DXA evaluation. The high prevalence of MBD in IF patients undergoing long-term treatment with PN requires that these patients undergo careful and periodic monitoring of their bone mineral status; patients with congenital gut dysfunctions, such as epithelium defects and motility anomalies, are at major risk of developing this complication, probably due to the association with extra-intestinal causes of bone loss.     

Distribution and characterization of cyclo (His-Pro)-like immunoreactivity in the human gastrointestinal tract

Cyclo (His-Pro) [C(HP)] has been measured by radioimmunoassay in perchloric acid extracts of human gastrointestinal (GI) tract structures derived from autopsy sources and fresh colonic biopsies. C(HP) was identified in all regions of the human GI tract, ranging in concentrations from 599 +/- 102 pg/mg protein in stomach, to 127 +/- 26 pg/mg protein in esophagus. The mean concentration of C(HP) from colonic biopsies was 335 +/- 30 pg/mg protein, statistically similar to values derived from postmortem sources. Since C(HP) concentrations are within the range of other gut peptide modulators, cyclo (His-Pro) is speculated to play a role as a new paracrine modulator of human GI tract function(s).     

Early emergence of PNH-like T cells after allogeneic stem cell transplants utilising CAMPATH-1H for T cell depletion

CAMPATH-1H (C-1H) is widely used in vivo and / or in vitro for T cell depletion in hematopoietic SCT. This humanised monoclonal antibody is specific for CD52, a marker coexpressed on the majority of human lymphocytes with CD48 and other glycosylphosphatidyl-inositol (GPI) anchored proteins. We detected CD52 / CD48 dual expression on >99% of CD3(+) lymphocytes from normal individuals and all 15 post-SCT patients whose transplants did not utilise C-1H. By contrast, 23 / 26 patients with transplants involving C-1H (in vivo, in vitro or both) exhibited populations lacking CD52 expression that accounted for 49.7% (4.2-86.2%) of the CD3+ lymphocytes (median and range) in samples evaluated at a median of 2 months post-SCT. Most CD52- cells also lacked CD48 expression. These GPI- T cells were of either donor or mixed donor / recipient origin. They were predominant in the early months after SCT at times of profound lymphopenia and inversely correlated with the recovery of the absolute lymphocyte count (r= - 0.663, P<0.0001). The presence of CD52- cells has been correlated previously with clinical outcome after CAMPATH therapy for both malignant and nonmalignant diseases.     

Independent FHC-related cardiac troponin T mutations exhibit specific alterations in myocellular contractility and calcium kinetics

Mutations in cardiac troponin T (cTnT) are linked to a severe form of Familial Hypertrophic Cardiomyopathy. Patients carrying mutations flanking the tropomyosin-binding domain of cTnT (R92L and Delta160E) develop distinct clinical syndromes. In order to better understand the cellular pathophysiology underlying these clinically relevant differences, we studied isolated adult left ventricular myocytes from independent transgenic cTnT mouse lines carrying either a 35% (Delta160E) or 50% (R92L) replacement of the endogenous cTnT with the mutant forms. Measurement of baseline myocellular contraction revealed that the Delta160E cells had significant decreases in the peak rate of contraction and percent shortening as compared to either R92L or Non-TG myocytes. In addition, while both Delta160E and R92L myocytes demonstrated a decrease in the peak rate of relaxation as compared to Non-TG, the magnitude of the difference was significantly greater in Delta160E cells. Concurrent myocyte [Ca2+](i) transient measurements revealed that while the alterations in the peak rates and times of the rise and decline of the [Ca2+](i) transient were similar to the changes in the respective measures of sarcomeric mechanics, R92L cells also exhibited reduced rates of the rise and decline of the [Ca2+](i) transient but did not exhibit these reductions in terms of sarcomeric mechanics. Of note, only Delta160E, and not R92L myocytes, demonstrated significant reductions in SR Ca2+ load and uptake, corresponding to the impairments seen in the [Ca2+](i) and mechanical transients. Finally, Western analysis revealed a significant Delta160E-specific reduction in the SERCA2a/PLB ratio, which may well underlie the observed alterations in Ca2+ homeostasis. Therefore, independent cTnT mutations result in significant mutation-specific effects in Ca2+ handling that may, in part, contribute to the observed clinical variability in cTnT-related FHC.     

Association between gastroesophageal reflux and endobronchial carcinoid: a case report

Children with neurological disorders may suffer from gastroesophageal reflux disease (GERD). Typical symptoms are vomiting, regurgitation and hematemesis. Patients present with respiratory symptoms only in cases with swallowing disorders causing chronic airway aspiration. We report the case of a patient affected by chromosome 8 p deletion syndrome with mental retardation, referred to our unit for suspected GERD. Chest X-ray, performed at admission for coexisting respiratory complaints, showed left lower lobe pneumonia; esophageal pH monitoring and upper endoscopy were normal for GERD. To rule out chronic airway aspiration, gastroesophageal 99 mTc scintigraphy with lung scan 18 to 24 h after a test meal and video fluoroscopy swallowing study were performed, both negative. Two months later, a second episode of left lower lobe pneumonia occurred. A chest CT scan was performed and showed an endobronchial mass; the biopsy taken during the broncoscopy was not conclusive. Surgical excision resulted in a diagnosis of pulmonary carcinoid. Bronchial carcinoids, although rare, should be taken into consideration as a potential cause of recurrent pneumonia even in the presence of demonstrated GERD where severe respiratory infections only occur with coexisting chronic pulmonary aspiration, even in neurologically impaired people.     

Chronic pancreatitis as presentation of Crohn’s disease in a child

It is reported that a pancreatic disease may precede the diagnosis of inflammatory bowel disease(IBD) both in children and in adults.Idiopathic chronic pancreatitis,however,occasionally co-exists with the IBD,mainly at pediatric age.We report a case of a patient who progressively developed the features of a chronic pancreatitis,before the diagnosis of Crohn’s Disease(CD).Ten months after the onset of the first episode of pancreatitis the patient developed bloody diarrhea,mucus stools and biochemical findings of inflammation.The colonoscopy revealed a diffuse colitis without involvement of the last loop and the gastroscopy showed inflammation of the iuxta-papillary area.The histological findings confirmed the diagnosis of CD that involved the colon and the duodenum.In conclusion,in children the idiopathic chronic pancreatitis may be an unusual presentation of CD.Thus,if other known cause of chronic pancreatitis are not found,a not invasive work up to exclude the IBD should be warranted.An early coincidental diagnosis of the IBD may delay the progression of the pancreatic disease.     

Characterization of gastric mucosal lesions in patients with celiac disease: a prospective controlled study

OBJECTIVE: Several studies have demonstrated that chronic exposure to gluten may damage the structure and function of the gastric mucosa in gluten-sensitive patients. However, until now, these abnormalities have been incompletely studied. Our purpose in the present study was to characterize, in a prospective controlled study, the endoscopic and histological appearance of the gastric mucosa in a large cohort of patients with celiac disease with and without Helicobacter pylori (H. pylori) infection. METHODS: We evaluated biopsy specimens taken from the gastric body and antrum of 218 individuals who underwent upper endoscopy for small bowel biopsy. One hundred-four patients had celiac disease (80 of them at the time of diagnosis-untreated). In 114 subjects celiac disease was excluded. RESULTS: Endoscopic findings did not show a difference between the groups. The prevalence of cases with normal gastric mucosa, chronic superficial gastritis, and atrophic gastritis was similar in patients and controls. Similarly, presence of metaplasia, inflammatory activity, and lymphoid follicles and aggregates did not show differences between the groups. Histological or serological evidence of H. pylori infection was detected in 86% of patients (82% of untreated celiacs and 95% of those on those taking treatment). The infection was highly prevalent in patients (89%) and controls (97%) diagnosed with chronic gastritis. Untreated patients had a significant greater IEL count in the antrum and corpus than controls (p < 0.0001 and p < 0.001, respectively). A global analysis of the data on intraepithelial lymphocyte (IEL) counts in the different populations suggest that the inflammatory state may represent the cumulative effect of H. pylori infection and gluten sensitivity. Only three patients had IEL infiltration compatible with diagnosis of lymphocytic gastritis (count >25%) and three other patients had borderline counts. CONCLUSIONS: According to our results, celiac disease patients presented a similar prevalence of gastric mucosal abnormalities compared with the control population. Evidence of H. pylori infection was very high compared with the prevalence in the general Argentine population. As a particular observation in our celiac population, the disease was rarely associated with lymphocytic gastritis. We suggest that the chronic inflammatory state evidenced by a gastric mucosal lymphocyte infiltration may be secondary to the combination of H. pylori infection and chronic gluten ingestion in gluten-sensitive subjects.     

Multicentre comparison of the antihypertensive effect of acebutolol and hydrochlorothiazide in uncomplicated mild-moderate hypertension in the elderly

Summary To evaluate the efficacy of acebutolol, 400–600 mg/day in elderly hypertensive patients, and to compare it with hydrochlorothiazide 25–50 mg/day, 45 patients with mild-moderate uncomplicated hypertension were treated for 6 weeks in a multicentre, single-blind, randomized, crossover trial. Acebutolol decreased supine systolic blood pressure from 186.5 to 162.7 mmHg and diastolic blood pressure from 107.4 to 92.4 mmHg. Hydrochlorothiazide decreased systolic blood pressure from 185.0 to 166.4 and diastolic blood pressure from 107.2 to 96.4. There was no difference between the effects of acebutolol and hydrochlorothiazide on blood pressure during the trial. Both drugs proved to be safe and effective antihypertensive agents, provided the major contraindications for their use were taken into account. Beta-blockade by acebutolol was highly effective in treating mild-moderate arterial hypertension in the elderly.     

Postoperative troponin T elevation as a predictor of early acute kidney injury after orthotopic liver transplantation: a preliminary retrospective study

Background

Slight alterations in cardiac enzymes are frequently observed perioperatively among liver transplant patients. The significance of these changes in the absence of ongoing acute cardiac pathology is unknown. We sought to evaluate the link between early postoperative anomalies of serum cardiac troponin T (cTnT) in the absence of an evident cardiac cause and kidney injury during the first week of hospital stay.

Methods

We retrospectively enrolled 30 patients in the study, recording several perioperative variables, particularly cTnT on intensive care unit ICU arrival as well as 6 and 12 hours later. We grouped patients with cTnT levels >0.03 ng/mL as the high-TnT group; the others were control subjects. We recorded the highest serum creatinine, aspartate aminotransferase, alanine aminotransferase, and bilirubin levels during the first week of the hospital stay. Glomerular filtration rate (GFR) was calculated according to the Cockroft-Gault formula.

Results

Ten patients composed the high-TnT group. Their perioperative variables showed higher Model for End-Stage Liver Disease (MELD) scores and significantly greater incidences of acute kidney injury, failure, and dialysis need than control patients. GFR dropped from 118 to 66 mL/min among this group versus 112 to 105 mL/min in control subjects (P = .021). Binary logistic regression analysis revealed a higher association between the high-TnT group and acute kidney injury (P = .036) than with the MELD score (P = .719).

Conclusions

Serum cTnT levels could be influenced by both preoperative and intraoperative conditions that predispose to kidney injury.     

Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL)

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01302-y.