SARS-CoV-2 infection in adult liver transplantation recipients: a systematic review of risk factors for mortality and immunosuppression role.

OBJECTIVE: Data on mortality, immunosuppression, and vaccination role regarding liver transplant (LT) recipients affected by COVID-19 are still under debate. This study aims to identify risk factors for mortality and the role of immunosuppression in COVID-19 LT recipients. MATERIALS AND METHODS: A systematic review of SARS-CoV-2 infection in LT recipients was performed. The primary outcomes were risk factors for mortality, the role of immunosuppression and vaccination. A meta-analysis was not performed as there was a different metric of the same outcome (mortality) and a lack of a control group in most studies. RESULTS: Overall, 1,343 LT recipients of 1,810 SOT were included, and data on mortality were available for 1,110 liver transplant recipients with SARS-CoV-2 infection. Mortality ranged between 0-37%. Risk factors of mortality were age >60 years, Mofetil (MMF) use, extra-hepatic solid tumour, Charlson Comorbidity Index, male sex, dyspnoea at diagnosis, higher baseline serum creatinine, congestive heart failure, chronic lung disease, chronic kidney disease, diabetes, BMI >30. Only 51% of 233 LT patients presented a positive response after vaccination, and older age (>65y) and MMF use were associated with lower antibodies. Tacrolimus (TAC) was identified as a protective factor for mortality. CONCLUSIONS: Liver transplant patients present additional risk factors of mortality related to immunosuppression. Immunosuppression role in the progression to severe infection and mortality may correlate with different drugs. Moreover, fully vaccinated patients have a lower risk of developing severe COVID-19. The present research suggests safely using TAC and reducing MMF use during the COVID-19 pandemic.

Phenotype/genotype correlation and cystic fibrosis related diabetes mellitus (Italian Multicenter Study).

BACKGROUND: A genotype/phenotype correlation between early onset cystic fibrosis related diabetes (CFRD) and the N1303K mutation of the CF gene was previously identified in a small series of 28 CFRD patients, out of 313 CF patients. PATIENTS AND METHODS: In order to confirm the observation, data of 141 CFRD patients out of 1,229 CF patients attending 14 Italian CF centers were collected. All patients were older than 10 years and had been genotyped. RESULTS: DeltaF508 was the most frequent mutation (147/282 alleles: 52%) and N1303K the second most frequent mutation (18/282 alleles: 6.3%) in CFRD patients, without significant difference as compared with CF patients without DM (52% vs 48.6% and 6.3% vs 5.1%, respectively). W1282X was the third most frequent mutation in CFRD patients, more frequent than in CF patients without DM (5.3% vs 2%; p<0.001). CONCLUSIONS: Unlike the previous study, we did not find a higher frequency of the N1303K mutation in CFRD patients; moreover, data from this large CF series showed a significant correlation between the W1282X mutation and CFRD.

Multievoked potentials in type I diabetic patients: one year follow-up study.

A neurophysiological (SEP, VEP) follow-up study was carried out in 30 diabetic patients with type I diabetes mellitus of ten or more years duration. This in order to investigate whether one year of improved glucoregulation may influence the progression of central damage. In our series, patients showed a significant decrement of HbA1C levels (p < 0.05) in the one-year follow-up. In the same period the frequency of SEP and VEP abnormalities varied from 10/30 (33%) to 16/30 (53%) and from 8/30 (26%) to 5/30 (16%) respectively. This finding would suggest that prevailing glycaemic control would be a major determinant for the outcome of VEP measurements. SEP alterations, in contrast, tend to progress in a 12 months period despite a considerable improvement in glycaemic control. However, by dividing patients in two groups according mean one year HbA1C less than 8% and more than 8%, the latter group only showed a significant increasing of absolute latencies of each median and tibial SEP components. Our results suggest that VEP abnormalities are still reversible in diabetic patients with improved metabolic control. The acquired abnormalities of somatosensory pathways persist longer, but a strict glycaemic control may influence and retard the progression of central conduction involvement.

Somatosensory and visual evoked potentials study in young insulin-dependent diabetic patients.

To evaluate central nervous system involvement in diabetes, somatosensory (SEPs) and visual (VEPs) evoked potentials were investigated in a group of 35 patients and 20 sex, age-matched controls. In order to avoid methodological biases due to different type and duration of disease, we studied an omogeneous group of young insulin-dependent diabetics with ten or more year duration of disease. In our results VEP and SEP parameters were found abnormal in 10 (28%) patients, all of whom presenting clear signs of peripheral neuropathy. In diabetic patients median and tibial SEPs showed significant increase in absolute latency mean values of several components except interpeak intervals, as well as mean P 100 latencies were significantly increased in both eyes at 15' check size stimulation pattern. VEP and SEP components were not generally significantly associated with the indices of peripheral function. In contrast, in diabetics significant correlations were found between P 100 latencies and median SEP parameters including interpeak intervals. No major associations related VEP and SEP latencies to duration of diabetes and prevailing glycaemic control. In conclusion the central nervous system involvement in young insulin-dependent diabetics, even though diffusely present, seems unequivocally concomitant to peripheral conduction impairment.

Nerve conduction velocity and circulating immunocomplexes in type 1 diabetic children.

There is evidence from several laboratories of an increased prevalence of circulating immuno-complexes (CIC) in diabetic patients. It has also been suggested that CIC are pathogenetically related to chronic diabetic complications. The aim of this study was to assess peripheral nerve function in children with Type 1 diabetes and to evaluate the relationship between the neurophysiological abnormalities and the possible presence of CIC. The investigation was carried out in 25 Type 1 diabetic patients ranging in age from 7-19 years and in 20 normal controls. Neurophysiological assessment was performed to evaluate motor and sensory conduction velocity on median and tibial nerves. IgG-CIC were detected by the solid-phase C1q-binding and anti-C3 enzyme immuno-assay. The results of this study showed a greater slowing of median motor and sensory and tibial sensory conduction velocities in patients with CIC with respect to the patients without CIC, suggesting a possible role of immunological factors in the pathogenesis of diabetic neuropathy.

Conduction velocity study in type 1 diabetic patients.

The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the peripheral nerve function and the influence of hyperglycemia on nerve conduction in insulin-dependent diabetes, a one-year neurophysiological study was carried out in 30 type 1 diabetic patients ranging in age from 2-16 years. During the 12-month follow-up period the glycosylated hemoglobin determination, motor conduction velocity of the peroneal nerve and the motor and sensory conduction of the tibial nerve were assessed 3 times, at the beginning of the study and every 6 months thereafter. The sensory latency was found significantly delayed in these patients as compared with the controls. The degree of sensory conduction slowing correlated well with the glycosylated hemoglobin concentrations and improved with the reduction in hyperglycemia.

Cross-reactivity of anti-ssDNA antibodies with heparan sulfate in patients with type I diabetes mellitus.

Anti-single-stranded-DNA antibodies cross-reactive with heparan sulfate were detected in serums of patients with type I (insulin-dependent) diabetes mellitus. The results suggested that heparan sulfate, the major glycosaminoglycan constituent of the glomerular basement membrane, may serve as a target antigen in vivo for cross-reactive anti-DNA antibodies. These polyreactive antibodies, directed toward repeating negatively charged units, may neutralize the heparan sulfate-associated polyanionic sites in the glomerulus, leading to an abnormal permeability of anionic plasma proteins.

The relationship of insulin antibodies, platelet-fixing immune complexes and platelet-associated IgG to in vitro platelet aggregation and thromboxane B2 synthesis in childhood type 1 (insulin-dependent) diabetes mellitus.

The relationship of insulin antibodies, platelet-fixing soluble immune complexes and platelet associated IgG to in vitro platelet aggregation and thromboxane B2 synthesis was studied in a group of children with type 1 (insulin-dependent) diabetes mellitus. Insulin antibodies, through the formation of insulin anti-insulin platelet-fixing immune complexes, seem to increase the levels of platelet associated IgG and both insulin immunity and increased platelet associated IgG are associated with the highest degree of platelet aggregation and thromboxane synthesis. These data suggest a possible role of immune factors in the platelet disfunction of diabetic subjects. Both platelet abnormalities and immune factors have been thought to play a role in the pathogenesis of the late diabetic complications. In this paper data concerning a possible interaction between these two factors are presented.

[Velocity of nerve conduction in children and adolescents with type I diabetes mellitus: clinical, metabolic and immunologic correlations]. / La velocità di conduzione nervosa in bambini ed adolescenti diabetici di I tipo: correlazioni cliniche, metaboliche ed immunologiche.

Clinical, metabolic, neurophysiologic and immunological data were obtained in a group of 50 patients with type I diabetes mellitus Results were compared with those obtained in 30 healthy subjects of comparable age. M.N.C. (median nerve conduction) velocities and sensitive latency were observed to be significant lower in the diabetic patients rather than in the controls. These abnormalities were correlated with the duration of diabetes rather than with the glucose control. The positivity for circulating immune complexes was found to be associated with a significant reduction of median sensory nerve conduction velocity. There results suggest that in addition to metabolic, genetic, vascular and hormonal abnormalities also immunologic factors may play a role in the pathogenesis of diabetic neuropathy.

[Vaginal infections in a population of diabetic children and adolescents]. / Infezioni vaginali in una popolazione di bambine e adolescenti diabetiche.

The prevalence of vaginal infections has been evaluated in 51 patient affected by insulin-dependent diabetes (IDDM) and in a control group of girls matched for age. Most frequent infectious agents were Candida Albicans (42.8%) and Streptococcus B (28.5%). No statistical significant relationship was observed between infection and duration of diabetes nor metabolic control, while the relationship was positive between infection and puberty. The peculiarity of this infection during IDDM is stressed and the difficulties in the infection when caused by Streptococcus B are discussed.

Circulating immune complexes and platelet thromboxane synthesis in patients with insulin-dependent (type I) diabetes mellitus.

Platelets from diabetic subjects with circulating immune complexes (CIC) synthesized greater amounts of thromboxane than did platelets from CIC-negative patients or controls. In view of the known action of CIC on platelet function, a relationship between these two factors may be suggested in the initiation and progression of microangiopathy in diabetes.

Platelet thromboxane synthesis in treated childhood diabetes mellitus.

TXB2 formation in PRP after thrombin or arachidonic acid stimulation was determined in 23 young compensated insulin-dependent diabetic patients, and in 10 control subjects of equivalent age. No significant difference in TXB2 synthesis during the times sampled was observed. Six out of 23 diabetics had circulating immune complexes (CIC) in their sera as detected by the C1q-SP; after the addition of arachidonic acid and thrombin the amount of TXB2 in PRP from CIC-positive patients was significantly higher than in PRP from CIC-negative patients. The increased synthesis of PG endoperoxides in CIC-positive patients could be a direct effect of antigen-antibody complexes on platelets.