Limited value of zinc protoporphyrin as a marker of iron status in chronic hemodialysis patients

BACKGROUND: In an attempt to find new parameters able to evaluate the actual iron availability by bone marrow cells, zinc protoporphyrin (ZnPP), a metabolic intermediate generated in the red blood cell by the incorporation of zinc instead of iron, has been proposed. ZnPP is a good marker of iron-deficiency anemia in non-uremic people, as red blood cell ZnPP concentration rises specifically (except for lead intoxication) in this condition. Existing data on ZnPP as a marker of iron deficiency in uremic patients comes mainly from cross sectional studies on chronic hemodialysis and has produced conflicting results. SUBJECTS AND METHODS: Therefore, we prospectively studied 42 HID patients, 28-88 years old, 13-346 months of dialysis age, beginning from a period of maximal iron deficiency, due to the lack of parenteral iron compounds (T0) up to the end of more than one year of follow-up with continuous parenteral iron supplementation (T4). ZnPP, hemoglobin, transferrin saturation and ferritin were serially determined before and after six weeks (T1), four months (T2), seven months (T3) and 14 months (T4) of parenteral iron supplementation at a maintenance dose of 0.5-1 mg/kg/week. RESULTS: In comparison with baseline values (95+/-37 micromol/mol heme) there were no significant changes in ZnPP levels at T1 and T2 despite a continuous increase in both transferrin saturation and ferritin values, while ZnPP significantly decreased at T4 (63+/-37 micromol/mol heme, p<0.001). There was no correlation between ZnPP and both transferrin saturation and ferritin at any time during the study, the same was true for ZnPP and zinc and lead serum concentration, fibrinogen and reactive C protein levels at T1 and T4, respectively. At T4, only 2/10 patients who still showed ZnPP levels >80 micromol/mol heme had absolute or functional iron deficiency, when the percentage of hypochromic red cells were measured. CONCLUSION: We conclude that ZnPP untimely parallels a change in iron balance in only a proportion of uremic people, in as much as confounding factors, such as chronic inflammation and uremia in itself may obscure its relationship with iron status. Therefore, ZnPP cannot be assumed to be a first-line diagnostic marker of iron balance in uremic patients.     

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region,Italy

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson’s correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.     

Nosocomial outbreak by NDM-1-producing Klebsiella pneumoniae highly resistant to cefiderocol,Florence, Italy,August 2021 to June 2022

A nosocomial outbreak by cefiderocol (FDC)-resistant NDM-1-producing Klebsiella pneumoniae (NDM-Kp) occurred in a large tertiary care hospital from August 2021–June 2022 in Florence, Italy, an area where NDM-Kp strains have become endemic. Retrospective analysis of NDM-Kp from cases observed in January 2021–June 2022 revealed that 21/52 were FDC-resistant. The outbreak was mostly sustained by clonal expansion of a mutant with inactivated cirA siderophore receptor gene, which exhibited high-level resistance to FDC (MIC ≥ 32 mg/L) and spread independently of FDC exposure.     

Gender effect on onset,prevalence and surgical treatment of cataract in patients with Myotonic Dystrophy type 1

Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, affecting 1:8000 individuals. It is a multi-systemic disorder involving muscle, heart, endocrine and respiratory apparatus and eye. The eye symptoms can include ptosis, external ophthalmoplegia, epiphora, and early onset cataracts. Cataracts occur at a much earlier age (usually between 30 and 40) than the general population, where females are usually affected more than men. We studied gender differences in cataract prevalence and treatment age in 243 DM1 patients (134 M; 109 F), aged 18 to 70 years, who were subsequently screened at routine follow-up. For each patient, information was collected on age, sex, CTG expansion, age of cataract onset, and age at cataract surgery, when available.Seventy-three patients, 30 females and 43 males, had cataracts, at a mean age of onset of 41.14 ± 12.64 in females, and 40.36 ± 10.03 in males. Sixty-nine of them underwent cataract surgery, males at an earlier age than females (42.8 ± 9.8 years versus 47.3 ± 12.6 years) and in 52.5% of cases before the age of 40, compared to 17.2% of females. The difference was statistically significant. The assumption that females in general and those with DM1 in particular develop cataracts more frequently and earlier than males is not confirmed, at least in this study. A possible explanation for these results could be related to non-advanced age, the protective role of estrogen and the lower prevalence of smoking in the study population.Key words: Myotonic Dystrophy type 1, Steinert disease, gender, cataract, cataract surgery, prevalence     

Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development

Temporal lobe epilepsy often manifests months or even years after an initial epileptogenic insult (e.g., stroke, trauma, status epilepticus) and, therefore, may be preventable. However, no such preventive treatment is currently available. Aim of this study was to test an antioxidant agent, 7,8-dihydroxyflavone (7,8-DHF), that is well tolerated and effective in preclinical models of many neurological disorders, as an anti-epileptogenic drug. However, 7,8-DHF also acts as a TrkB receptor agonist and, based on the literature, this effect may imply an anti- or a pro-epileptogenic effect. We found that low- (5 mg/kg), but not high-dose 7,8-DHF (10 mg/kg) can exert strong anti-epileptogenic effects in the lithium-pilocarpine model (i.e., highly significant reduction in the frequency of spontaneous seizures and in the time to first seizure after status epilepticus). The mechanism of these different dose-related effects remains to be elucidated. Nonetheless, considering its excellent safety profile and antioxidant properties, as well as its putative effects on TrkB receptors, 7,8-DHF represents an interesting template for the development of effective and well-tolerated anti-epileptogenic drugs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01299-4.     

Transplacental passage of Pt after treatment with the new triamine complex cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate,N<Superscript>4</Superscript>]-chloride platinum (II) monohydrochloride monohydrate

Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N⁴]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a monofunctional Pt triamine complex synthesized starting from cisplatin and procaine hydrochloride, characterized by a good antitumor activity coupled with low toxic effects and able to impair prenatal development of mice but at doses outside or just in the upper range of therapeutic doses. In the present paper the transplacental passage of DPR-derived Pt was investigated in CD1 mice on days 9, 13, 16 and 18 of pregnancy, 24 h after ip administration of 21 mg/kg DPR. For comparison, groups of mice were treated with an equivalent Pt-containing dose of cisplatin (10.7 mg/kg). Similarly to cisplatin, small amounts of Pt were detected in fetuses on day 9. From day 13 of gestation the concentration of DPR- and cisplatin-derived Pt increased up to the highest fetal concentrations detected on day 16. On day 18 the concentration of Pt decreased. Most importantly, on days 13–18 of pregnancy cisplatin-derived Pt was always significantly higher than that assayed after DPR administration. In addition, on day 13 of pregnancy Pt exposure of fetuses was significantly higher when dams were treated with cisplatin (AUC_0.5–24= 3.40 vs. 4.95 g·h/g). Finally, it is worth noting that serum decay of Pt after DPR or cisplatin administration in adult female mice was similar with AUC_0.13–2h s of 7.5 and 6.6 g·h/ml, respectively. When we determined the concentration of Pt into the main organs of fetuses from dams treated with either DPR or cisplatin on day 18 of gestation, we observed a different organ distribution. In fact, while the concentration of DPR-derived Pt was greater in the heart (1.08±0.30 vs. 0.78±0.35 g/g, p <0.10), an opposite situation was found in the kidney (0.51±0.20 vs. 0.69±0.22 g/g, p <0.05). In conclusion, our data show that DPR may pass through the placenta with an efficiency significantly lower than that of cisplatin. This finding may represent one of the possible causes of the lower embryotoxic/teratogenic effect of DPR as compared to cisplatin.     

Ascites,pleural, and pericardial effusions in acute pancreatitis

Ascites and pleural and pericardial effusions can be observed during acute pancreatitis. The aims of this study were to evaluate their incidence, natural history, and prognostic role in patients with acute pancreatitis. One hundred patients consecutively admitted with a diagnosis of acute pancreatitis were prospectively submitted to abdominal, pleural, and cardiac ultrasonography at admission and during follow-up. Ascites was found in 18 patients, pleural effusion in 20, and pericardial effusion in 17. Twenty-four patients of this series had severe pancreatitis; three of them died. All effusions disappeared spontaneously in patients who survived pancreatitis up to two months after dismissal. At multivariate analysis ascites and pleural effusion were demonstrated to be accurate independent predictors of severity. The respective odds ratios were 5.9 [95% confidence interval (CI), 1.5–23.0%) and 8.6 (95% CI, 2.3–32.5%). Furthermore the presence of pleural effusion, ascites, and pericardial effusion were associated with an increased incidence of pseudocyst during follow-up. Ascites and pleural and pericardial effusions are frequent during acute pancreatitis. Pleural effusion and ascites are accurate predictors of severity in these patients.