Transient plasma viral rebound after SARS-CoV-2 vaccination in an exceptional HIV-1 elite controller woman.

BACKGROUND: Elite controllers are able to control viral replication without antiretroviral therapy. Exceptional elite controllers do not show disease progression for more than 25 years. Different mechanisms have been proposed and several elements of both innate and adaptive immunity are implicated. Vaccines are immune stimulating agents that can promote HIV-RNA transcription; transient plasma HIV-RNA detectability has been described within 7-14 days after different vaccinations. The most reliable mechanism involved in virosuppressed people living with HIV is a generalized inflammatory response that activates bystander cells harboring latent HIV. So far no data about viral load increase in elite controllers after SARS-CoV-2 vaccination are reported in literature. CASE PRESENTATION: We report the case of a 65-year-old woman of European ancestry, diagnosed with HIV-1/HCV co-infection more than 25 years ago. Since then, HIV-RNA remained undetectable and she never received ARV therapy. In 2021 she was vaccinated with mRNA-BNT162b2 vaccine (Pfizer-BioNTech®). She was administered with three doses in June, July and October 2021, respectively. The last available viral load was undetectable in March 2021. We observed an increase of VL at 32 cp/ml and 124 cp/mL, two and seven months after the second vaccine dose, respectively. During monthly follow-up, HIV-RNA gradually and spontaneously dropped becoming undetectable without ARV intervention. COVID-19 serology was positive with IgG 535 BAU/mL, showing response to vaccination. We measured total HIV-DNA at different time-points and we found it detectable both at the time of the higher plasma HIV-RNA (30 cp/10^6 PBMCs) and when it was undetectable (13 cp/10^6 PBMCs), in reduction. CONCLUSIONS: This case is the first report, to our knowledge, describing a rebound of plasma HIV-RNA in an elite controller after three doses of mRNA-BNT162b2 vaccine for SARS-CoV-2. Concomitantly with a spontaneous reduction of plasma HIV-RNA ten months after the third dose of mRNA-BNT162b2 vaccine (Pfizer-BioNTech®) without antiretroviral therapy intervention, we observed a reduction of total HIV-DNA in peripheral mononuclear cells. The potential role of vaccinations in altering HIV reservoir, even in elite controllers when plasma HIV-RNA is undetectable, could be a valuable aspect to take into account for the future HIV eradication interventions.

Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

Metastatic volume: an old oncologic concept and a new prognostic factor for stage IV melanoma patients.

BACKGROUND: The last melanoma staging system of the 2009 American Joint Committee on Cancer takes into account, for stage IV disease, the serum levels of lactate dehydrogenase (LDH) and the site of distant metastases. OBJECTIVE: Our aim was to compare the significance of metastatic volume, as evaluated at the time of stage IV melanoma diagnosis, with other clinical predictors of prognosis. METHODS: We conducted a retrospective multicentric study. To establish which variables were statistically correlated both with death and survival time, contingency tables were evaluated. The overall survival curves were compared using the Kaplan-Meier method. RESULTS: Metastatic volume and number of affected organs were statistically related to death. In detail, patients with a metastatic volume >15 cm(3) had a worse prognosis than those with a volume lower than this value (survival probability at 60 months: 6.8 vs. 40.9%, respectively). The Kaplan-Meier method confirmed that survival time was significantly related to the site(s) of metastases, to elevated LDH serum levels and to melanoma stage according to the latest system. CONCLUSION: Our results suggest that metastatic volume may be considered as a useful prognostic factor for survival among melanoma patients.

Psoriasis vulgaris does not adversely influence the quality of sleep.

AIM: Sleep could be severely affected in psoriasis because of skin symptoms and psychological repercussions of the disease. The aim of this study was to investigate the influence of psoriasis on sleep. METHODS: A total of 202 patients with psoriasis and 202 healthy volunteers have completed a self-rated questionnaire, the Pittsburgh Sleep Quality Index, which assesses sleep quality and disturbances over a 1-month time interval. The severity of the dermatoses has been evaluated utilizing the PASI score. RESULTS: In psoriatic patients the Pittsburgh Sleep Quality Index resulted between 0 and 17 (5.56±3.93), in the controls between 0 and 18 (5.13±4.16). No statistically significant correlation was observed between the score of Pittsburgh Sleep Quality Index and PASI. The anti-psoriatic therapy, while causing a marked improvement of lesions and itching, does not affect the quality of sleep. CONCLUSION: Although literature indicated that psoriasis negatively affects the quality of sleep, in this study this correlation was not observed.

The east-west advancement flap (horizontal advancement flap) to repair a defect on the nose ala.

BACKGROUND: The repair of an alar nasal defect is a frequent challenge for dermatologic surgeons for reasons of the high rate of non-melanoma cancers in the area. OBJECTIVE: Our aim was to describe the use of an east-west cheek-based flap (horizontal advancement flap) to repair a surgical defect on the nose ala. METHODS: Benefits and limits of this surgical procedure are evaluated. RESULT: The resulting S-shaped scar was well-camouflaged among the natural skin lines (melolabial fold and melonasal junction). No architectural distortion of the nose resulted from the procedure. CONCLUSION: In selected patients with small-to-medium-size defects of the nasal ala, the horizontal advancement flap is a simple, reliable and aesthetic reconstruction option.

Pulmonary sarcoidosis in a patient with psoriatic arthritis during infliximab therapy.

The occurrence of sarcoidosis during anti-TNF-alpha therapy has occasionally been published. We report the case of a psoriasis patient who developed pulmonary sarcoidosis during a cycle of therapy with infliximab.

[Minimally invasive video-assisted parathyroidectomy and intraoperative parathyroid hormone monitoring]. / Paratiroidectomia mini-invasiva video-assistita e monitoraggio intraoperatorio del paratormone.

BACKGROUND: Aim of this study is to analyze our preliminary results from minimally invasive video-assisted parathyroidectomy (MIVAP) and to evaluate the clinical impact of intraoperative measurements of intact parathyroid hormone (PTHIO). PATIENTS AND METHODS: MIVAP by an anterior approach was proposed for patients with sporadic primary hyperparathyroidism pHPT and one unequivocally enlarged parathyroid gland on preoperative ultrasound and 99mTc-SestaMIBI scintigraphy. We used an operative technique first described by Miccoli in 1997, without carbon dioxide insufflation. Quick parathyroid hormone immunochemiluminometric assay (qPTHa) was performed intraoperatively during all surgical procedures. Age, operative times, pathologic findings, postoperative pain, calcemia, length of hospital stay, cosmetic results, and complications were retrospectively analyzed. RESULTS: From October 2006 to December 2009, MIVAP was proposed for 28 of 40 (70%). Mean operative time was 65 minutes. Postoperative complications included 4 (12.9%) transient hypocalcemia and one (3.22%) transient nerve palsy with complete recovery. No definitive laryngeal nerve palsies, no definitive hypocalcemias, no persistent pHPT and no recurrent pHPT were observed. The cosmetic result was excellent in all cases. CONCLUSIONS: Our preliminary results demonstrate that MIVAP for localized single-gland adenoma, after adequate training, seems to be feasible with significant advantages, especially in terms of cosmetic results, postoperative pain, and postoperative recovery, if performed by dedicated team, with a sufficient and specific activity volume.

Non-randomized pilot study on the evaluation of the quality of life and psychosocial stress before and after systemic therapy in patients affected by moderate to severe psoriasis.

Psoriasis has a major impact on patients? lives, affecting them physically, psychologically and socially. The aim of this study is to investigate psoriasis in relation to quality of life and psychological stress in two groups of patients treated with biologics and narrow-band UVB, respectively. We conducted a nonrandomized, prospective, comparative pilot study on 40 patients suffering from moderate to severe psoriasis. The comparison of the delta score of Skindex-29, Psoriasis Life Stress Inventory and the PASI at baseline and at the end of the treatment in the two groups highlighted the variation of the Psoriasis Life Stress Inventory which resulted significantly higher (P<0.001) in the group treated with biologics. The ease of administrating the combination Etanercept and Efalizumab, with consequent reduction of stress levels, attains a better control of psoriasis compared to phototherapy.

Minimally invasive video-assisted parathyroidectomy. Initial experience in a General Surgery Department.

BACKGROUND: The aim of this study is to analyze our preliminary results from minimally invasive video-assisted parathyroidectomy (MIVAP) and demonstrate the feasibility of MIVAP also in non-referral centers. MATERIAL AND METHODS: During a period from June 2005 to January 2008, in the General Surgery Department of University of Trieste, we operated on 39 patients with primary hyperparathyroidism (pHPT). MIVAP by an anterior approach was proposed for 23 (59%) patients with sporadic pHPT and one unequivocally enlarged parathyroid gland on pre-operative ultrasound and 99mTc-SestaMIBI scintigraphy without associated goiter and without previous neck surgery. Intra-operatively, a quick parathyroid assay was used during the last 11 surgical procedures. All patients underwent pre-operative and post-operative investigations of calcemia, phoshoremia and PTH levels and vocal cord function. Age, operative times, pathologic findings, post-operative pain, calcemia, length of hospital stay, cosmetic results, and complications were retrospectively analyzed. RESULTS: MIVAP was successfully accomplished in 22 cases. Conversion to standard cervicotomy was required in one patient (4.34%). Mean operative time was 67 min. Post-operative complications included 1 (4.34%) transient hypocalcemia. No laryngeal nerve palsies, no definitive hypocalcemias, no persistent pHPT and no recurrent pHPT were observed. The cosmetic result was excellent in all cases. CONCLUSIONS: Our preliminary results demonstrate that MIVAP for localized single-gland adenoma, after adequate training, seems to be feasible with significant advantages, especially in terms of cosmetic results, post-operative pain, and post-operative recovery even in a General Surgery Department, if performed by a dedicated team, with a sufficient and specific activity volume.

Idiopathic mesenteric venous thrombosis: report of a case.

INTRODUCTION: Idiopathic mesenteric venous thrombosis is a rare entity. An early diagnosis and thrombolytic and anticoagulant therapy are very important. PATIENT AND METHODS: We report a case of a patient, without any specific known risk factor, with small intestinal ischemia secondary to superior mesenteric vein thrombosis (SMVT). RESULTS: In our case, only a computed tomography (CT) abdominal scan permitted the diagnosis of SMVT. The patient was successfully treated by resection of the infarcted bowel with primary anastomosis and immediate postoperative anticoagulation. CONCLUSIONS: Diagnosis of intestinal ischemia from mesenteric venous thrombosis (MVT) is often delayed because the symptoms are nonspecific. Moreover, when there is not any known predisposing factor, the diagnosis may become even more difficult with significant morbidity and mortality. CT abdominal scan done early in case of nonspecific abdominal pain, since the patients had a previous history of venous thrombosis, may not require a surgical treatment of MVT.

Redox proteomics and immunohistology to study molecular events during ischemia-reperfusion in human liver.

Oxidative stress is a condition occurring in liver disorders and causing liver damage due to ischemia-reperfusion (I/R) during liver transplantation. Several markers of chronic oxidative stress are well known; however, early protein targets of oxidative injury are not well defined. To identify them, we used a differential proteomics approach to HepG2 human liver cells that has been treated for 10 minutes with 500 micromol/L H(2)O(2). By differential proteomic analysis, using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, we identified four proteins sensitive to H(2)O(2) treatment that underwent posttranslational modification of native polypeptides. Three of the proteins belong to the Peroxiredoxin family of hydroperoxide scavengers, PrxI, PrxII, and Prx VI, that showed changes in their pI as result of hyperoxidation. Mass mapping experiments demonstrated specific modification of the peroxiredoxins active site thiol into sulphinic and/or sulphonic acid, thus explaining an increased negative charge. The oxidation kinetics of all peroxiredoxins were extremely rapid and sensitive, occurring at H(2)O(2) doses unable to affect common markers of cellular oxidative stress. A differential proteomics approach was also applied to liver needle biopsies after cold (T(1)) and warm (T(2)) ischemia. Proteomic analysis of this material was related to histological changes and immunophenotypic expression of APE1/Ref-1. Hyperoxidation of PrxI occurring during I/R upon liver transplantation is dependent on the time of warm ischemia. Histological changes and APE1/Ref-1 expression parallel Peroxiredoxin changes. Our present data may be relevant to better graft preservation and evaluation for transplantation.

The role of hepatic biopsy to detect macrovacuolar steatosis during liver procurement.

The ability to predict graft function before transplantation has proven to be a difficult task, especially for macrovacuolar steatosis that is considered a major cause of posttransplant dysfunction. It is well known that macrovacuolar steatosis greater than 25% influences the short- and long-term outcomes of liver transplantation. We retrospectively analyzed frozen sections from 43 donor livers comparing preoperative laboratory/clinical values, and liver ultrasound of a cohort of donors without (group A, n=21) versus with steatosis of 25% to 35% (group B, n=22) upon liver biopsy performed during harvesting. We analyzed the possible correlations between preoperative donor data and the degree of macrovacuolar steatosis. None of the biochemical and clinical parameters were related to the degree of hepatic steatosis. The only difference between the two groups was the echographic pattern, with evidence of 27% fatty liver by ultrasound in group B and 5% in group A (p=.04). The specificity of hepatic ultrasound for macrovacuolar steatosis was 95% and the sensitivity was only 27%, while the positive and negative predictive value were 86% and 55%, respectively. In conclusion, liver biopsy during donor harvesting remains the gold standard to identify macrovacuolar steatosis greater than 25%. Hepatic ultrasound has a role to exclude the presence of steatosis in normal livers due to its high specificity, but it is not useful to make the diagnosis of a fatty liver since it has a low sensitivity and negative predictive value. Thereafter a liver ultrasound positive for hepatic steatosis alone should not be considered a valuable tool to discard an organ from transplantation.

Characterization of the first tick isolate of Borrelia burgdorferi from Italy.

We report on the first isolation of a spirochetal organism from Ixodes ricinus ticks of the Trieste area (Northern Italy) which was identified as Borrelia burgdorferi by its reactivity with specific monoclonal antibodies directed against the OSPA and flagella proteins.

Lyme arthritis presenting as adult onset Still's disease.

Lyme disease and adult onset Still's disease share several clinical characteristics such as fever, lymphosplenomegaly, skin involvement, and arthritis. Borrelia burgdorferi has been recognized as the cause of Lyme disease and an infectious agent has been suspected, at least as triggering factor, in adult onset Still's disease. This work is concerned with a patient affected by atypical Lyme disease originally diagnosed as adult onset Still's disease. B. burgdorferi infection must be suspected in cases of arthritis suggestive of adult onset Still's disease.

DNA repair investigations in nine Italian patients affected by trichothiodystrophy.

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair, mental and growth retardation, peculiar face, ichthyosis, and in 20% of the reported cases photosensitivity. Cellular photosensitivity due to the same genetic defect present in xeroderma pigmentosum group D (XP-D) has been described in several patients. Nine patients with clinical symptoms diagnostic for TTD have been identified in Italy to date. We report the results of DNA repair investigations performed in cultured fibroblasts from these patients and 8 TTD parents. Survival, DNA repair synthesis and RNA synthesis following UV irradiation were all normal in the 8 TTD heterozygous cell strains. Among the 9 TTD-affected individuals, normal cellular UV sensitivity was observed in the 2 patients without signs of clinical photosensitivity. In contrast, the other 7 TTD cell strains showed a notable reduction in UV-induced DNA repair synthesis (UDS) levels, ranging between 40% and 5-15% of normal values. Complementation analysis indicated that in the repair-deficient TTD cell strains the genetic defect is the same as that present in XP-D cells. The biochemical heterogeneity of the XP-D defect in TTD patients characterized by different degrees of defective UDS results in different patterns of response to the killing effect of UV light in non-proliferating cells.