Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19.

The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.

Delayed Surgical Treatment of a CE1 Lung Cyst Resulting in Pericystectomy of CE4 Cyst.

Lung is the second most common locationof cystic echinococcosis (CE), after the liver. Diagnosis of lung CE is often incidental, and clinical manifestations depend on the location and size of the cyst, the most common being chest pain, shortness of breath, expectoration of fragments of endocyst, and haemoptysis. Surgery is the primary treatment, with a minor role for medical therapy. Delayed diagnosis and treatment may have important consequences. We present a case of lung CE in whichsurgical treatment was delayed due to the first wave of COVID-19. Since surgery could not be performed immediately, the patient was kept on albendazole and the cyst stage moved from CE1 to CE3a, to CE4, eventually requiring a more aggressive pericystectomy instead of the commonly performed endocystectomy. The clinical and imaging characteristics of a rare CE4 cyst of the lung are reported.

Visceral larva Migrans in a Young Italian Patient: A Diagnostic Dilemma.

BACKGROUND: The association of fever, focal hepatic lesions and peripheral hyper-eosinophilia (FHLH) can be observed in both infectious and non-infectious conditions. Fascioliasis, capillariasis, toxocariasis, all causes of visceral larva migrans (VLM), represent most of the former, whilst lymphomas, eosinophilic leukemias and mastocytosis belong in the non-infectious conditions. METHODS: We prospectively followed a young patient presenting with FHLH in the Tuscany region of Italy. RESULTS: The patient was subject to serological and parasitological examination in an attempt to clarify the origin of the lesions. Serologies for both Fasciola hepatica and Toxocara spp. were positive, with the latter presenting a higher index. We opted for treatment with a prolonged course of albendazole due to the serological results and being toxocariasis more frequent in our setting. The patient was then subject to radiological follow-up. The patient responded to treatment with albendazole as shown by a decrease in eosinophils, seronegativization for Toxocara spp., clinical and radiological improvement. Toxocariasis was hence considered the most likely diagnosis. CONCLUSIONS: Parasitic infections cannot be disregarded in the presence of FHLH. Differential diagnosis between these parasitic infections can be challenging due to the presence of similar clinical presentations and serological cross-reactions, and follow-up of the patient is needed to ensure optimal treatment outcomes.

The high burden of pediatric cystic echinococcosis in Kazakhstan: epidemiological and clinical consequences.

BACKGROUND: Cystic echinococcosis (CE) is attributable to Echinococcus granulosus metacestodes. Ultrasound examinations enable a stage-specific approach to CE management. However, this approach is not often applied in endemic areas, which include Kazakhstan. METHODS: We collected clinical and ultrasound data on CE pediatric patients seen at a national referral surgical center in Almaty, Kazakhstan, during 2015-2020. RESULTS: We included 49 patients, and 79 cysts that were all surgically treated. All but one patient carried active cysts (CE1-CE3 stages). Twenty-six (53.2%) did not receive albendazole postsurgery. Children with CE1 and CE3a cysts underwent surgery, while the use of albendazole and percutaneous drainage were advised upon by experts. CONCLUSIONS: A stage-specific approach to CE management in Kazakhstan is urgent, especially in the pediatric population. The rate of active cysts suggests continuing transmission of CE.

Scalp eschar and neck lymph adenopathy after a tick bite (SENLAT) in Tuscany, Italy (2015-2022).

INTRODUCTION: The Scalp Eschar and Neck Lymph Adenopathy After a Tick Bite (SENLAT) syndrome is frequently caused by Rickettsia slovaca and Rickettsia raoultii. Only six microbiologically confirmed SENLAT cases have been reported in Italy between 1996 and 2021. We report ten cases of SENLAT seen between 2015 and 2022 in a tertiary care center in Tuscany, Italy. CASES PRESENTATION: All patients were women; most common symptoms were scalp eschar on the site of tick bite (100%) and cervical lymphadenopathy (90%). No microbiological identification was obtained. Persistent alopecia, for several months to years, was observed in four patients. The known difficulty of microbiological diagnosis in SENLAT was worsened, in our cases, by factors as the absence of ticks available for identification and microbiological study, and antibiotic treatment administration previous to microbiological tests. CONCLUSION: The report highlights the presence of SENLAT in Italy, aiming to raise the awareness toward the emergence of this clinical entity.

Diagnosis and management of complicated urogenital schistosomiasis: a systematic review of the literature.

BACKGROUND: Currently, there are no standardized guidelines for the diagnosis or management of the complications of urogenital schistosomiasis (UGS). This systematic review of the literature aims to investigate the state of the art in reference to diagnostic approaches and the clinical management of this condition. METHODS: A systematic review of literature published between January 1990 and January 2021 was conducted in the MEDLINE database, scoping for articles regarding diagnostic means or therapeutic options for the complications of UGS, namely obstructive uropathy, bladder cancer, abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures. Relevant data were then extracted from the articles deemed eligible according to the inclusion criteria. MAIN RESULTS: In total, 3052 articles were identified by the research query, of which 167 articles fulfilling inclusion criteria after title/abstract screening and full-text evaluation were included, 35% on both diagnostic and therapeutic aspects, and 51% on diagnosis and 14% on therapy. Ultrasound was the most frequently tool employed for the diagnosis of UGS complications showing a good performance. Concerning the management of hydronephrosis, the majority of available evidences came from community-based studies where universal treatment with praziquantel was used leading to decrease of prevalence of obstructive uropathy. Concerning studies on surgical procedures, laser endoureterotomy followed by stenting was mostly employed in adult patients leading to a crude cure rate of 60% (43 of 71 patients). In the case of severe hydronephrosis, surgery consisting of ureteral re-implantation showed excellent results with a crude cure rate of 98% (157 cured patients of 160 treated). Concerning bladder cancer, data on 93 patients with a clear diagnosis of UGS-related bladder were available reporting a variable and sometime combined approach based on disease stage. Available data on diagnosis and management of abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures due to UGS are also presented. CONCLUSIONS: The review produced a complete picture of the diagnostic and therapeutic options currently available for complicated UGS. These results can be useful both for guiding clinicians towards correct management and for tracing the direction of future research.

Seroconversion following empiric praziquantel treatment as confirmatory diagnostic tool for chronic schistosomiasis.

We report on six patients with suspected chronic schistosomiasis and negative microbiological findings at baseline. All patients were treated empirically with praziquantel and all seroconverted 20 days to two months after treatment. We suggest that seroconversion after praziquantel treatment may be used as a confirmatory diagnostic tool for chronic schistosomiasis.

Ultrasound-Based Prevalence of Cystic Echinococcosis in the Samarkand Region of Uzbekistan: Results from a Field Survey.

Cystic echinococcosis (CE) is a zoonosis caused by Echinococcus granulosus. Uzbekistan is endemic for CE, but estimates of disease burden are lacking. We present findings from a cross-sectional, ultrasound-based survey evaluating the prevalence of human CE in the Samarkand region, Uzbekistan. The survey was conducted between September and October 2019 in the Payariq district, Samarkand. Study villages were selected based on sheep breeding and reported human CE. Residents aged 5-90 years were invited to receive a free abdominal ultrasound examination. The WHO Informal Working Group on Echinococcosis classification was used for cyst staging. Information regarding CE diagnosis and treatment was collected. Of 2,057 screened subjects, 498 (24.2%) were male. Twelve (0.58%) had detectable abdominal CE cysts. In total, five active/transitional (N = 1 CE1, N = 1 CE2, N = 3 CE3b) and 10 inactive cysts (N = 8 CE4, N = 2 CE5) were identified. Two participants had cystic lesions with no pathognomonic features of CE and were given a 1-month course of albendazole for diagnostic purposes. Twenty-three additional individuals reported previous surgery for CE in the liver (65.2%), lungs (21.6%), spleen (4.4%), liver and lungs (4.4%), and brain (4.4%). Our findings confirm the presence of CE in the Samarkand region, Uzbekistan. Additional studies are needed to assess the burden of human CE in the country. All patients with a history of CE reported surgery, even though most cysts found during the current study were inactive. Therefore, it appears there is a lack of awareness by the local medical community of the currently accepted stage-specific management of CE.

Circulating Small RNA Profiling of Patients with Alveolar and Cystic Echinococcosis.

Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Characteristics of COVID-19 vaccinated and unvaccinated patients admitted to Careggi University Hospital, Florence, Italy.

More than 11.5 billion COVID-19 vaccine doses have been administered around the world. Although vaccine effectiveness for severe infections is reported to be 89.0%, breakthrough infections are common and may lead to severe outcome in fragile population. We conducted a real-world observational study on 420 COVID-19 admitted patients from July 2021 to January 2022 in a tertiary level Italian hospital. We collected patient's vaccination and SARS-CoV-2 serological status, SARS-CoV-2 treatments, oxygen supports, intensive (ICU) and subintensive (sub-ICU) care unit admissions, length of staying (LoS) and in-hospital mortality. One-hundred-seventy-two vaccinated and 248 unvaccinated patients were admitted during the study period. Vaccinated group (Vg) had a significantly more elevated Charlson Comorbidity Index than Unvaccinated group (UVg), and no statistical differences were found in terms of in-hospital mortality, LoS or ICU and sub-ICU admissions. Among Vg, anti-S antibodies were detected in 86.18% of patients (seropositives). Vaccinated seronegative patients' in-hospital mortality was significantly higher than vaccinated seropositive patients (33.33% vs 10.69%, p = 0.0055): in particular, mortality rate in 45-69 years old population was higher in vaccinated seronegative group, and comparable in patients ≥ 70 years old. No differences in terms of outcome were registered between Vg and UVg, taking into account that Vg was considerably older and with more comorbidities. In line with other recent observations, higher mortality rate was evidenced for seronegative vaccinated patients. Primary prophylaxis and early treatments result to be necessary, especially for older and immunosuppressed populations.

Benign liver lesions 2022: Guideline for clinical practice of Associazione Italiana Studio del Fegato (AISF), Società Italiana di Radiologia Medica e Interventistica (SIRM), Società Italiana di Chirurgia (SIC), Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB), Associazione Italiana di Chirurgia Epatobilio-Pancreatica (AICEP), Società Italiana Trapianti d'Organo (SITO), Società Italiana di Anatomia Patologica e Citologia Diagnostica (SIAPEC-IAP) - Part II - Solid lesions.

Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic hepatic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicated document. This document was drawn up according to the present Italian rules and methodologies necessary to produce clinical, diagnostic, and therapeutic guidelines based on evidence. Here we present the second part of the guideline, concerning the diagnosis and clinical management of hemangioma, focal nodular hyperplasia, and hepatocellular adenoma.

Benign liver lesions 2022: Guideline for clinical practice of Associazione Italiana Studio del Fegato (AISF), Società Italiana di Radiologia Medica e Interventistica (SIRM), Società Italiana di Chirurgia (SIC), Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB), Associazione Italiana di Chirurgia Epatobilio-Pancreatica (AICEP), Società Italiana Trapianti d'Organo (SITO), Società Italiana di Anatomia Patologica e Citologia Diagnostica (SIAPEC-IAP) - Part I - Cystic lesions.

Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicated document. This document was drawn up according to the present Italian rules and methodologies necessary to produce clinical, diagnostic, and therapeutic guidelines based on evidence. Here we present the first part of the guideline, concerning the characterization of focal hepatic lesions detected by ultrasound, and the diagnosis and clinical management of simple and parasitic hepatic cysts, and of polycystic liver disease.

Implementing Early Phase Treatments for COVID-19 in Outpatient Settings: Challenges at a Tertiary Care Center in Italy and Future Outlooks.

We present a brief commentary illustrating the current COVID-19 outpatient treatment options in Italy. We also report our experience setting up a service dedicated to these patients in the wake of the rise in COVID-19 cases observed in January 2022. We also gathered data on the daily costs faced by our outpatient service, based at a tertiary care center located in Florence, Italy. We present them with some considerations on future outlooks on the use of outpatient treatment in COVID-19.

Conservative Management of Liver Echinococcal Cysts in Pregnant Women: One Center's Experience in Pavia, Italy.

Human cystic echinococcosis (CE) in pregnancy is rarely reported, with approximately one case of CE for every 20,000 to 30,000 pregnant women in endemic areas. Little information on its management is available. We report our experience with a watch-and-wait approach in this group of patients. We retrieved clinical data from pregnant patients with hepatic CE seen at our clinic from 1989 to 2021. All patients had at least one hepatic CE cyst and received no treatment during pregnancy. Ultrasound was used to monitor cyst evolution; outcome and complications of pregnancy and echinococcal infection were evaluated. Twelve patients with 15 pregnancies were included in this study. At the time of pregnancy, nine patients had a single cyst and two patients had multiple hepatic CE cysts. Cysts were in stage CE3a, CE3b, CE4, and CE5, according to the WHO Informal Working Group on Echinococcosis classification. All cysts except one remained stable in stage and size during and after pregnancy. In one patient with a history of multiple treatments with albendazole and with a CE4 cyst at the start of pregnancy, reactivation of the cyst during pregnancy was observed. All pregnancies except three had eutocic delivery. Cesarean sections were performed for reasons unrelated to CE. In our experience, "watch and wait" in pregnant women with uncomplicated transitional and inactive CE of the liver was a safe option in a small cohort of patients. Pooled data from other referral centers, including cases with CE1 and CE2 cysts, are needed to confirm the safety of this approach.