Effect of antimetabolite regimen on cellular and humoral immune response to SARS-COV-2 vaccination in solid organ transplant recipients.

OBJECTIVE: Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity. METHODS: In this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients. RESULTS: Our results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients' ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination. CONCLUSION: These results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy.

Comparison of the efficacy, safety and durability of a switch to co-formulated RPV/TDF-TAF/FTC or DTG/ABC/3TC in virologically-suppressed HIV-1-infected patients in a single Italian centre: a cohort data analysis.

This study evaluated the efficacy, safety and durability of a switch to co-formulated RPV/TDF-TAF/FTC (RPV-STR) or DTG/ABC/3TC (DTG-STR) in virologically-suppressed HIV-positive patients in a single Italian centre. All HIV-infected ART-experienced patients switching to RPV-STR or DTG-STR with HIV-RNA <50 copies/mL were included. Outcomes were incidence rate and rate ratios for discontinuation due to all causes (DAC), to adverse events (DAE) and to virological failure (VF) after 4 years of follow-up. We included 402 patients (244 on RPV-STR, 158 on DTG-STR). At Year 4 of follow-up, 124 patients (30.8%) discontinued for any cause (71 on RPV-STR, 53 on DTG-STR). Fifteen patients experienced VF [13 (5.3%) on RPV-STR and 2 (1.3%) on DTG-STR; log-rank, P = 0.4413]. Overall, 46 patients (11.4%) had AEs (23 on RPV-STR, 23 on DTG-STR). Nausea/diarrhoea was more frequent with DTG-STR (4.4% vs. 0%) and neurological toxicity with RPV-STR (4.5% vs. 2.5%). The rate of DAC within the first 3 months was significantly higher with DTG-STR (aRR = 5.88, 95% CI 3.20-10.81; P < 0.001); similarly, the discontinuation rate due to AEs was significantly higher with DTG-STR compared with RPV-STR (aRR = 12.89, 95% CI 5.48-30.32; P < 0.001). No difference in VF was observed between the two groups (RR = 0.47, 95% CI 0.10-2.14; P = 0.335). Patients with undetectable viral load who switched to DTG-STR or RPV-STR maintained virological suppression with a low risk of VF. A higher discontinuation rate was observed with DTG-STR compared with RPV-STR, particularly within 3 months from switch.

Ceftolozane/tazobactam for Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis adult patients: a case series.

Management of cystic fibrosis (CF) patients colonized with Pseudomonas aeruginosa is challenging due to its virulence and multi-drug resistance. Ceftolozane/tazobactam (C/T) is a promising new antipseudomonal agent, and clinical data on CF are limited. We describe our experience in the use of C/T for P. aeruginosa-related pulmonary exacerbations (PE) in CF adults admitted within 2016 and 2019 at Careggi Hospital, Florence, Italy. PE was diagnosed as deterioration of respiratory function, worsening cough, and increasing of sputum. C/T was given at the dose of 3 g every 8 h. C/T was used in ten patients. Mean length of C/T treatment was 16.3 days, and tobramycin was the most frequently combined antipseudomonal agent. All patients were successfully treated although susceptibility testing on sputum sample showed C/T resistance in two cases. No adverse effects related to C/T were reported. To our knowledge this is the largest case series on CF patients treated with C/T. Clinical responses were encouraging even where C/T resistant P. aeruginosa was isolated, probably due to multiple phenotypes colonizing CF lungs. C/T could play a promising role in combination therapy against P. aeruginosa as a part of a colistin-sparing regime.

The Risks of Complications During Endoscopic Sinus Surgery in Cystic Fibrosis Patients: An Anatomical and Endoscopic Study.

OBJECTIVE/HYPOTHESIS: An increasing proportion of adult cystic fibrosis (CF) patients is being referred to endoscopic sinus surgery (ESS) in order to relieve the symptoms of chronic rhinosinusitis (CRS). Given that CFTR mutations profoundly alter sinonasal development, we want to explore the relationship between their peculiar surgical anatomy and the risk of postoperative complications. STUDY DESIGN: Retrospective case-control study. METHODS: Paranasal sinuses CT scans of 103 CF adult patients with CRS were compared to those belonging to a cohort of 100 non-CF adult patients to explore their anatomical differences. Secondly, CF and non-CF patients who received primary/revision ESS were analyzed in order to assess their preoperative CT scan in terms of surgically relevant variants, and according to the CLOSE checklist. Surgical outcomes were statistically compared in order to explore the differences between groups. RESULTS: CF group presented more frequently with smaller and less pneumatized paranasal sinuses and a higher Lund-Mckay score compared with controls. No anatomical differences emerged in terms of genotype stratification. Non-CF CRS patients undergoing ESS showed a significantly deeper olfactory fossa and a more frequent supraorbital pneumatization compared to CF patients (P < .001 and P = .031, respectively). Whereas this latter group underwent more often aggressive surgical procedures (P = .001), no difference in terms of postoperative adverse events was found (P = .620). CONCLUSIONS: Despite receiving more often aggressive ESS procedures, adult CF patients do not show an increased risk of postoperative complication and this may be linked to a different proportion of anatomical and surgically-relevant variants. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2481-E2489, 2021.

Threatening drug-drug interaction in a kidney transplant patient with coronavirus disease 2019 (COVID-19).

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.

Short article: Safety of targeted prophylaxis strategy in patients with resolved hepatitis B virus infection receiving rituximab for immune-mediated diseases.

OBJECTIVES: Rituximab (RTX) is a monoclonal antibody that is widely used in hematologic malignancies and immune-mediated diseases (IMID) and has been associated with the risk of hepatitis B virus reactivation (HBVr). Thus, antiviral prophylaxis is recommended before RTX treatment in all patients with chronic hepatitis B virus (HBV) infection and those with resolved infection affected by onco-hematological conditions. By contrast, the correct management of HBsAg-negative/HbcAb-positive patients candidates for RTX-containing regimens for IMID is still debated, owing to few data currently available in this setting. PATIENTS AND METHODS: We retrospectively evaluated the risk of HBVr in patients with IMID with resolved HBV infection, referred to the Infectious and Tropical Diseases Unit Outpatients Service, Careggi Hospital, Florence, Italy, between September 2013 and September 2017, undergoing RTX without antiviral prophylaxis and followed up by serial serum HBV-DNA monitoring. RESULTS: Overall, 20 patients with IMID were identified (70% female, with median age of 57 years) and followed up for a median period of 19 months (range: 2-36 months). A single HBVr case, detected in preclinical stage, was observed (1/20, 5%), and targeted prophylaxis was promptly introduced. CONCLUSION: The results supported the low to moderate risk of HBVr in HBsAg-negative/HBcAb-positive patients with IMID undergoing RTX, in contrast to what is observed in onco-hematological settings. The targeted prophylaxis strategy, based on serum HBV-DNA serial monitoring, seems a safe option in these patients.

Serial QuantiFERON TB-gold in-tube testing during LTBI therapy in candidates for TNFi treatment.

OBJECTIVES: To evaluate the T-cell interferon (IFN)-γ response to Mycobacterium tuberculosis-specific antigens during latent tuberculosis infection (LTBI) therapy in candidates for tumor necrosis factor-α inhibitors (TNFi). METHODS: 1490 Patients were screened for LTBI. One-hundred and sixty-six of them were treated for LTBI and followed-up with QuantiFERON-TB Gold (QFT-IT) testing at baseline (T0) and therapy completion (T1); 92 subjects were also tested 3-6 months after therapy completion (T2). RESULTS: At T1 the QFT-IT reversion and conversion rates were 24% (27/111) and 18% (10/55), respectively. By multivariate analysis, the likelihood of reversion significantly decreased with older age (>50-60), larger TST size (>15 mm) and higher IFN-γ value at T0 (>1 IU/ml); the likelihood of conversion increased with higher IFN-γ levels at T0 (1 IU/ml) and in female patients. Quantitative data among those who scored QFT-IT-positive at T0 showed a decreasing trend of IFN-γ levels between T0 and T1 that reached statistical significance when T0 was compared to T2, and T1 to T2. CONCLUSIONS: The data confirm the difficulty of interpreting the modulation of IFN-γ levels during LTBI therapy. Currently, there is no evidence to support the use of QFT-IT in the clinical practice of monitoring LTBI treatment in candidates for TNFi.

Chronic hepatitis C virus hepatitis and psoriasis: no longer a contraindication to interferon use in the era of biological agents?

We describe a patient with severe psoriasis and hepatitis C simultaneously treated with pegylated interferon alpha (peg-IFNα) plus ribavirin and etanercept, whose skin lesions improved and who reached a sustained virological response. This case suggests that refractory psoriasis can today no longer be considered as a contraindication for combined hepatitis C virus treatment.

Hepatitis E virus genotype 3 in humans and Swine, Bolivia.

We determined the seroprevalence of hepatitis E virus (HEV) in persons in 2 rural communities in southeastern Bolivia and the presence of HEV in human and swine fecal samples. HEV seroprevalence was 6.3%, and HEV genotype 3 strains with high sequence homology were detected.

Current management of differentiated thyroid carcinoma.

Papillary and follicular thyroid cancers, together termed differentiated thyroid cancers (DTC), comprise the majority of thyroid carcinomas and have an optimal prognosis. Most DTCs appear as asymptomatic thyroid nodules. Fine-needle aspiration (FNA) cytology is the first diagnostic test for a thyroid nodule in a euthyroid patient. Surgery is the primary treatment for thyroid cancers. Most clinicians recommend near-total or total thyroidectomy, and then 131I ablation therapy, since its consequences are minimal and follow-up is facilitated. A total body scan (TBS) is performed 4 to 7 days after 131I treatment. At a later stage, all patients should be treated with L-tiroxine so as to suppress TSH, and must undergo a periodic evaluation of TSH and thyroglobulin (Tg), the most sensitive and specific marker of DTC. After 6-12 months, TBS with 131I is performed, a technique complementary to serum Tg evaluation. For this technique, it is also necessary to have a high serum TSH concentration, obtained by withdrawing thyroxine therapy for 4 to 6 weeks. This standard method induces hypothyroidism. An alternative method to the withdrawal of thyroid hormones in the follow-up of DTC patients is to administer recombinant human TSH (rh-TSH). After the dose of rhTSH, 131I is administered, and then TBS can be performed 48-72 hours later. Currently, several authors have explored the possibility that rh-TSH-stimulated Tg levels may represent the only necessary test to differentiate patients with persistent disease from disease-free patients, without performing a diagnostic TBS.