Ileorectal anastomosis in ulcerative colitis: what do surgeons and patients need to know? A systematic literature review.

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) is currently the gold standard for restoration of gastrointestinal continuity after colectomy for ulcerative colitis in the UK. However, with further experience of the risks relating to IPAA, the use of ileorectal anastomosis (IRA) is being revisited. Decisions regarding restorative surgery after colectomy are individual to every patient's circumstances, and this paper aims to provide a comprehensive review of the literature to guide a full discussion of the risks and benefits of IRA. METHODS: A systematic literature review was conducted of papers published from 2000 onwards relating to IRA and ulcerative colitis, in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The papers were reviewed by two independent surgeons for information it was felt that patients and surgeons would want to know about the operation (cancer risk, bowel function, sexual and urinary function, fecundity/fertility and postoperative complications). RESULTS: Seventeen papers were identified for inclusion as they reported original data on one or more of the categories identified for discussion. The median ten-year cancer risk after IRA was 2.8% and the median failure rate at ten years was 21%. IRA was generally found to have lower postoperative complication rates and better bowel function than IPAA, with sexual function similar and fecundity not commented on in any paper. CONCLUSIONS: For some patients, IRA can offer restorative surgery in the short or long term, with acceptable cancer risk, failure rate and postoperative complications, while avoiding the higher risks associated with IPAA.

Bamlanivimab and Etesevimab administered in an outpatient setting for SARS-CoV-2 infection.

The early administration of anti-SARS-CoV-2 monoclonal antibodies (mAb) could decrease the risk of severe disease and the need of inpatients care. Herein, our clinical experience with Bamlanivimab/Etesevimab for the treatment of early SARS-CoV-2 infection through an outpatient service was described. Patients with confirmed COVID-19 were selected by General Practitioners (GPs) if eligible to mAb administration, according to manufacturer and AIFA (Agenzia-Italiana-del-Farmaco) criteria. If suitability was confirmed by the Multidisciplinary Team, the patient was evaluated within the next 48-72 hours. Then, all patients underwent a medical evaluation, followed by mAb infusion or hospitalization if the medical condition had worsened. Overall, from March 29th to June 4th, 2021, 106 patients with confirmed COVID-19 were identified by GPs; 26 were considered not eligible and then excluded, while 9 refused treatment. Among the 71 remaining, 6 were not treated because of worsening of symptoms soon after selection. Finally, 65 received mAb therapy. All treated patients survived. However, 2/65 developed adverse events (allergic reaction and atrial fibrillation, respectively) and 6/65 needed hospitalization. By performing univariate logistic regression analysis, diabetes was the only risk factor for hospitalization after mAb administration [aOR = 9.34, 95%CI = 1.31-66.49, p= .026]. Importantly, subjects who worsened awaiting mAb were more frequently obese (OR = 16.66, 95%CI = 1.80-153.9, p= .013) and received home corticosteroid therapy for COVID-19 (OR = 14.11, 95%CI = 1.53-129.6, p= .019). Establishing a network among GPs and COVID units could be an effective strategy to provide mAb treatment to patients with early SARS-CoV-2 infection to reduce hospitalizations and pressure on healthcare systems.

Peculiar clinical presentation of COVID-19 and predictors of mortality in the elderly: A multicentre retrospective cohort study.

BACKGROUND: The spectrum of COVID-19 clinical manifestations is not yet known. In the elderly, mortality and extrapulmonary involvement appears more frequent than expected. METHODS: A multicentre-retrospective-case-series study of COVID-19 patients, aged ≥65 years, hospitalised between March 1 and June 15, 2020. Patients were classified at admission into 3 groups based on their Clinical Frailty Scale (CFS) score: 1-3 (group A), 4-6 (group B) and 7-9 (group C). RESULTS: Of the 206 patients in the study, 60 (29%) were assigned to group A, 60 (29%) to B and 86 (42%) to C. Significantly more frequent in group C than in B or A were: mental confusion (respectively 65%, 33%, 7%; P < 0.001), kidney failure (39%, 22%, 20%; P = 0.019), dehydration syndrome (55%, 27%, 13%; P < 0.001), electrolyte imbalance (54%, 32%, 25%; P = 0.001), and diabetic decompensation (22%, 12%, 7%; P = 0.026). Crude mortality was 27%. By multivariate logistic regression model independent predictors of death were male sex (adjusted odds ratio (aOR) = 2.87,95%CI = 1.15-7.18), CFS 7-9 (aOR = 9.97,95%CI = 1.82-52.99), dehydration at admission (aOR = 4.27,95%CI = 1.72-10.57) and non-invasive/invasive ventilation (aOR = 4.88,95%CI = 1.94-12.26). CONCLUSIONS: Elderly patients with a high CFS showed frequent extrapulmonary signs at admission, even in the absence of lung involvement. These findings, along with a high CFS, predicted a significant risk of mortality.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide or dual therapy-based regimens in HIV-infected individuals with viral load ≤50 copies/mL: does estimated glomerular filtration rate matter?

Our aim was to evaluate the association between recent eGFR values and risk of switching from TDF to TAF or dual therapy (DT) in real life. HIV-positive patients achieving HIV-RNA ≤50 copies/mL for the first time after starting a TDF-based regimen were included. Kaplan-Meier (KM) curves and Cox regression models were used to estimate the time from TDF to switch to TAF or DT. 1486 participants were included: median (IQR) age 36 (30-42) years; baseline CKD-EPI eGFR 99.92 (86.47-111.4) mL/min/1.73m2. We observed a consistently higher proportion of people with HIV-RNA ≤50 copies/mL who switched from TDF to TAF rather than to DT. By competing risk analysis, at 2 years from baseline, the probability of switching was 3.5% (95% CI 2.6-4.7%) to DT and 46.7% (42.8-48.5%) to TAF. A significantly higher probability of switching to TAF was found for patients receiving INSTI at baseline versus NNRTIs and PI/b [KM, 65.6% (61.7-69.4%) vs. 4.0% (1.8-6.1%) and 59.9% (52.7-67.2%), respectively; P < 0.0001]. eGFR <60 mL/min/1.73m2 both as time-fixed covariate at baseline or as current value was associated with a higher risk of switching to DT [aHR 6.68 (2.69-16.60) and 8.18 (3.54-18.90); P < 0.001] but not to TAF-based cART [aHR 0.94 (0.39-2.31), P = 0.897; and 1.19 (0.60-2.38), P = 0.617]. Counter to our original hypothesis, current eGFR is used by clinicians to guide switches to DT but does not appear to be a key determinant for switching to TAF.

Maternal caesarean section infection (MACSI) in Sierra Leone: a case-control study.

Sierra Leone is the country with highest maternal mortality and infections are the underlying cause in 11% of maternal deaths, but the real burden remains unknown. This study aims to determine the incidence and risk factors of surgical site infection (SSI) post-caesarean section (CS) in women admitted to Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone. A prospective case-control (1:3 ratio) study was implemented from 1 May 2018 to 30 April 2019 and 11 women presenting with suspected or confirmed infection post-CS were screened for inclusion as a case. For each case, three patients undergoing CS on the same day and admitted to the same ward, but not presenting with SSI, were selected as controls. The post-CS infection rate was 10.9%. Two hundred and fifty-four clinically confirmed cases were enrolled and matched with 762 control patients. By multivariable analysis, the risk factors for SSI were: being single (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.36-1.66), low education level (OR 1.68, 95% CI 1.55-1.84), previous CS (OR 1.27, 95% CI 1.10-1.52), presenting with premature membranes rupture (OR 1.49, 95% CI 1.18-1.88), a long decision-incision time (OR 2.08, 95% CI 1.74-2.24) and a high missing post-CS antibiotic doses rate (OR 2.52, 95% CI 2.10-2.85).

Management of cutaneous manifestations of lupus erythematosus: A systematic review.

BACKGROUND: Cutaneous lupus erythematosus (CLE), occurring with or without systemic lupus erythematosus (SLE), is a group of inflammatory skin diseases that can be very debilitating, causing significant psychological distress, and sometimes scarring. OBJECTIVES: We sought to comprehensively present the evidence for different treatment modalities in patients with cutaneous manifestations of lupus erythematosus (LE). METHODS: Medline, Embase, Scopus and Cochrane CENTRAL were searched electronically from 1990 to March 2019, using keywords related to cutaneous lupus and synonyms and treatment. Articles retrieved were screened for relevance, including reference lists of retrieved reviews. We included clinical trials, observational studies or case series with ≥5 patients focussing on treatment of CLE, with or without SLE. RESULTS: The search identified 6637 studies, of which 107 were included. Each study commonly included a heterogeneous mixture of CLE subtypes, with or without SLE. The 107 included studies investigated 11 different categories of treatment in 7343 patients. Treatments included topical calcineurin inhibitors (13 studies), sun protection (5 studies), R-salbutamol cream (2 studies), antimalarials (22 studies), synthetic DMARDs (10 studies), retinoids (2 studies), thalidomide/lenalidomide (22 studies), biologic therapies (15 studies), intravenous immune globulin (3 studies), laser (6 studies) and other therapies (7 studies). General measures to be considered include smoking cessation, sun protection measures and optimisation of vitamin D levels. Moderate evidence exists for benefit with topical CNIs, particularly as a steroid sparing agent in areas at high risk of steroid complications (e.g. facial skin). There is moderate evidence for hydroxychloroquine, which is first-line in SLE patients, limited evidence to support other synthetic DMARDs, and moderate evidence supporting thalidomide but with significant risk of toxicity. Of biologic therapies, there are moderate data to support belimumab. Limited evidence exists for other therapies. CONCLUSION: Many management options are available for CLE, including topical, systemic and biologic therapies, with a variable balance of efficacy and toxicity. There is a paucity of high-quality clinical trial data. Further trials are required to better understand optimal management of CLE, particularly in specific subgroups.

Splenic abscesses as a first manifestation of Crohn's disease: a case report.

BACKGROUND: Splenic nodules are uncommon entities that occur rarely in the general population. Although an infectious etiology (primarily bacteria, followed by mycobacteria) is usually found, noninfectious diseases, including malignancies and autoimmune disorders, can also be involved. For instance, in course of inflammatory bowel diseases (IBDs), in particular Crohn's Disease, aseptic splenic abscesses have been reported in patients with a long history of illness, or in those unresponsive to medical treatments, while are only anecdotally reported in the early phase of the disease. Hence, we presented the case of aseptic splenic nodules as a first manifestation of Crohn's Disease. CASE PRESENTATION: A 21-year-old woman with a silent medical history was admitted to the Emergency Department of our hospital complaining of fever of 38-39 °C (mainly in the evening) for the past 10 days and left flank abdominal pain, accompanied by sweating and fatigue. An abdominal computed tomography showed multiple splenic nodules of unknown origin. Because of the absence of clinical improvement after several antibiotic therapiesand a positron emission tomography (PET) with hypercaptation strictly localized to spleen, she underwent splenectomy, in suspicion of lymphoma. For persistence of symptoms after splenectomy, she underwent many instrumental examination, including a colonoscopy with bowel and intestinal biopsies that poses diagnosis of Crohn's disease. A second PET confirmed this diagnosis showing this time also the gastrointestinal involvement. CONCLUSION: An unusual onset of Crohn's disease with multiple splenic nodules is reported. This case suggests that in light of splenic nodules of unknown etiology attention should be paid to all possible diagnoses of aseptic abscesses, including IBDs (primarily Crohn's Disease).

Cerebrospinal fluid compartmentalization of HIV-1 and correlation with plasma viral load and blood-brain barrier damage.

PURPOSE: We aimed to evaluate HIV-1 compartmentalization between the cerebrospinal fluid (CSF) and plasma and investigate as to which extent HIV-1 strains in CSF differ from those in blood and whether a correlation with either plasma viral load (pVL) or an altered blood-brain barrier (BBB) does exist. STUDY DESIGN: We retrospectively evaluated paired CSF/blood samples collected from 86 HIV+ patients. HIV-RNA quantification, pol (PR/RT), and V3 sequencing were performed. HIV coreceptor tropism (CRT) was inferred (g2p, false-positive rate 10%, FPR). Data of standard CSF analysis were also reviewed; an altered CSF/plasma albumin ratio signified BBB damage. Neurological abnormalities (NA) were recorded. RESULTS: Overall, 32% of patients had a CSF/plasma HIV-RNA ratio > 1 (discordance); 3% of patients had detectable CSF HIV-RNA despite suppressed pVL (escape). Discordance was more frequent in ART-treated patients (p < 0.001) and in patients with NA (p = 0.016), but was independent of BBB damage (p = 0.65) and AIDS diagnosis (p = 0.96). Finally, CSF/plasma discordance was significantly more frequent (p < 0.0001) in patients with lower pVL values (< 10.000 copies/ml). Env divergence > 10% was found in 44% of sequences and was associated with ART (p = 0.008) and NA (p = 0.037). Overall, 24% of patients had a discordant CSF/blood CRT. A 100% nucleotide identity was observed in only 7.3% of pol sequences; notably, 10% of patients had resistance-associated mutations in CSF, but not in blood. CONCLUSIONS: Our data confirm an independent replication and evolution of HIV within the CSF. A number of factors either hinder or contribute to the compartmentalization of HIV.

Kidney Transplantation in Alström Syndrome: Case Report.

The Alström syndrome is a rare genetic disorder, inherited in an autosomal recessive manner. It has recently been classified as a ciliopathic disorder. Alström syndrome is a multiorgan pathology characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, short stature in adulthood, hypothyroidism, hypogonadism, dilated or restrictive cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. End-stage renal disease can occur as early as the late teens and is the leading cause of death. More than 900 people with Alström syndrome have been reported worldwide. We present a case of a 42-year-old man affected by this syndrome with end-stage renal disease, type 2 diabetes mellitus, and loss of visual function and hearing who received a kidney transplant from a cadaveric donor. Basiliximab and steroid were used as induction therapy. Tacrolimus, mycophenolate mofetil, and steroid were used as maintenance therapy. No complications were reported during the recovery. In selected patients affected by Alström syndrome, renal transplantation can be a successful treatment for chronic kidney disease.

Reduced community viral load does not coincide with a reduction in the rate of new HIV diagnoses and recent infections: data from a region of southern Italy.

OBJECTIVES: We assessed whether changes in community viral load (CVL) over time were associated with the rate of new HIV diagnoses (NDs). METHODS: HIV-1-positive individuals referred to our institute and permanently residing in our province were considered for inclusion in the study. A total of 861 HIV-infected adults with at least one HIV RNA measurement (12 530 measurements in total) between 2008 and 2014 were included. Viraemia copy-years were calculated from all HIV RNA values for each patient using the trapezoidal rule; multiple CVL indicators were considered. Total NDs and recent infections (< 1 year) were analysed separately. The association between NDs and CVL was tested by means of mixed Poisson models, with CVL as a fixed effect and year as a random effect. RESULTS: The incidence of NDs was 2.28 per 100 000 residents in 2008 and 2.52 per 100 000 residents in 2014. Total numbers of NDs and recent infections did not vary significantly over time (P for trend 0.879 and 0.39, respectively). Mean HIV RNA decreased from 31 095.8 HIV-1 RNA copies/mL in 2008 to 21 231.5 copies/mL in 2014 (P < 0.001); a downward trend was always observed regardless of the CVL indicator considered. Depending on the indicator, there were some differences in CVL by patient characteristics. The most substantial contributors to CVL appeared to be male individuals, men who have sex with men (MSM), non-Italians, and untreated subjects (all P < 0.05). The relative risk of ND increased among Italians and MSM with an increasing proportion of subjects having an undetectable HIV RNA, and decreased in the same population with increasing levels of CVL. CONCLUSIONS: In our setting, CVL represented a good marker of access to care and treatment; however, reduced CVL did not coincide with a reduction in the rate of NDs.

The molecular pathogenesis of morphoea: from genetics to future treatment targets.

A number of immunoinflammatory and profibrotic mechanisms are recognized in the pathogenesis of broad sclerotic skin processes and, more specifically, morphoea. However, the precise aetiopathogenesis is complex and remains unclear. Morphoea is clinically heterogeneous, with variable anatomical patterning, depth of tissue involvement and sclerotic, inflammatory, atrophic and dyspigmented morphology. Underlying mechanisms determining these reproducible clinical subsets are poorly understood but of great clinical and therapeutic relevance. Regional susceptibility mechanisms (e.g. environmental triggers, mosaicism and positional identity) together with distinct pathogenic determinants (including innate, adaptive and imbalanced pro- and antifibrotic signalling pathways) are likely implicated. In the age of genetic profiling and personalized medicine, improved characterization of the environmental, systemic, local, genetic and immunopathological factors underpinning morphoea pathogenesis may open the door to novel targeted therapeutic approaches.

Severe recalcitrant cutaneous manifestations in systemic lupus erythematosus successfully treated with fumaric acid esters.

Fumaric acid esters (FAEs) have proven efficacy in the treatment of psoriasis and have been in use for decades. More recently, as their mechanism of action and abundant immunomodulatory effects become clearer, the potential benefits of treating other inflammatory skin conditions using FAEs are increasingly being recognized. The use of FAEs as combination systemic therapy has not been well studied and data are lacking regarding the safety and efficacy of this type of therapy. In this case report, three patients with severe, extensive and recalcitrant cutaneous manifestations of systemic lupus erythematosus (SLE) (one case of disseminated discoid lesions and two with severe chilblain lesions) were treated with Fumaderm® (containing the FAE dimethylfumarate and monoethylhydrogen fumarate salts), after failing to respond to a multitude of other monotherapies and combination therapies. All patients showed a substantial clinical response when FAEs were added to their treatment, with concurrent improvements in quality-of-life instrument scores. The treatment was well tolerated in the context of systemic organ involvement and as combination therapy with other agents, such as hydroxychloroquine and mycophenolate mofetil. These cases of SLE illustrate the potential use of FAEs in severe, disfiguring and otherwise therapy-resistant skin lesions, including, to our knowledge, the first two reported cases of FAE-treated chilblain lupus erythematosus.

CD4 and CD4/CD8 ratio progression in HIV-HCV infected patients after achievement of SVR.

BACKGROUND: In HIV-HCV co-infected patients, the long-term effects of HCV eradication on HIV disease progression are still unclear. OBJECTIVES: This study aims to determine if CD4 and CD4/CD8 ratio slopes improved after anti-HCV treatment in patients achieving a sustained virological response (SVR). STUDY DESIGN: A total of 116 HIV-HCV co-infected patients, previously treated with Peg-IFN/RBV, were divided into two groups: SVR (55 patients who had achieved SVR), and non-SVR (61 patients). Retrospective data before and after anti-HCV therapy were obtained for all patients, with a median 8 year-follow-up. Multilevel mixed models were fitted to assess the trends over time of FIB-4 score, APRI score, CD4, CD8 cell count and CD4/CD8 ratio. RESULTS: Median HIV-infection duration, HCV-RNA and GGT baseline levels were higher in non-SVR compared to the SVR group. A significantly decreased FIB-4 (p<0.001) and APRI trend (p<0.001) after SVR was observed in SVR patients compared to those non-SVR. After adjustment for HIV duration, there was no significant difference between the two groups for absolute CD4 (p=0.08) or percentage CD4 slope (p=0.6) over time. The CD4/CD8 ratio trend also demonstrated a similar progressive increase in both groups (p=0.2). During follow-up, six deaths were reported in the non-SVR group versus no death for the SVR group, while no difference in AIDS and non-AIDS events was observed. CONCLUSIONS: Achievement of SVR determines an important beneficial impact in terms of liver-related mortality and fibrosis regression, but does not seem to alter neither the slope of long term CD4 gain nor the CD4/CD8 ratio evolution in ART-treated HIV-HCV co-infected patients.

Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response.

Data on the effects of sustained virologic response (SVR) to hepatitis C virus (HCV) therapy on the outcome of extrahepatic complications are scarce. We conducted this study to assess the impact of SVR on the occurrence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of human immunodeficiency virus (HIV)-infected patients. We analyzed coinfected HIV/HCV patients in the Management of Standardized Evaluation of Retroviral HIV Infection (MASTER) cohort. Only event-free patients with a serum HCV-RNA determination at baseline were included. Patients were divided into four groups: INF-exposed with SVR; INF-exposed without SVR; spontaneous HCV clearance; untreated viremic patients. We estimated the incidence of extrahepatic complications and employed Kaplan-Meier curves and Cox regression to assess the association of SVR/INF strata adjusted for a series of confounders. Data from 1676 patients were analyzed (20.29 % started an INF-based regimen). Overall, the incidence of CKD, DM, CVD, and death was 5.32 [95 % confidence interval (CI) 3.99-6.98], 10.13 (95 % CI 8.20-12.37), 6.79 (95 % CI 5.26-8.65), and 13.49 (95 % CI 11.29-16.0) per 1000 person-years of follow-up, respectively. In the Cox model for treated patients, SVR was not associated with a lower risk of CKD, DM, CVD, and death compared to non-SVR. Cirrhosis was significantly associated with a higher risk of CKD [hazard ratio (HR) 2.13; 95 % CI 1.06-4.31], DM (HR 3.48; 95 % CI 2.18-5.57), and death (HR 6.18; 95 % CI 4.1-9.31), but not of CVD (HR 1.14; 95 % CI 0.57-2.3). There are still many unknowns regarding the impact of SVR on the occurrence of extrahepatic complications in coinfected HIV/HCV patients. Further investigations are needed in order to elucidate the role of SVR as an independent prognostic factor for extrahepatic events.