ABSTRACT
Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.
Subject(s)
Antiviral Agents , Hepatitis C, Chronic , Peripheral Nervous System Diseases , Humans , Male , Female , Middle Aged , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/virology , Prospective Studies , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Adult , HIV Infections/complications , HIV Infections/drug therapy , Prevalence , Hepacivirus/drug effects , Aged , Coinfection/drug therapy , Coinfection/virology , Risk Factors , Cryoglobulinemia/etiology , Sustained Virologic ResponseABSTRACT
BACKGROUND: Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease marker. There is a plethora of studies exploring associations between miscarriage and stillbirth with long-term adverse maternal health; however, these data are inconclusive. METHODS AND FINDINGS: We systematically searched MEDLINE, EMBASE, AMED, BNI, CINAHL, and the Cochrane Library with relevant keywords and MeSH terms from inception to June 2023 (no language restrictions). We included studies exploring associations between stillbirth or miscarriage and incidence of cardiovascular, malignancy, mental health, other morbidities, and all-cause mortality in women without previous pregnancy loss. Studies reporting short-term morbidity (within a year of loss), case reports, letters, and animal studies were excluded. Study selection and data extraction were performed by 2 independent reviewers. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) and publication bias with funnel plots. Subgroup analysis explored the effect of recurrent losses on adverse outcomes. Statistical analysis was performed using an inverse variance random effects model and results are reported as risk ratios (RRs) with 95% confidence intervals (CIs) and prediction intervals (PIs) by combining the most adjusted RR, odds ratios (ORs) and hazard ratios (HRs) under the rare outcome assumption. We included 56 observational studies, including 45 in meta-analysis. There were 1,119,815 women who experienced pregnancy loss of whom 951,258 had a miscarriage and 168,557 stillbirth, compared with 11,965,574 women without previous loss. Women with a history of stillbirth had a greater risk of ischaemic heart disease (IHD) RR 1.56, 95% CI [1.30, 1.88]; p < 0.001, 95% PI [0.49 to 5.15]), cerebrovascular (RR 1.71, 95% CI [1.44, 2.03], p < 0.001, 95% PI [1.92, 2.42]), and any circulatory/cardiovascular disease (RR 1.86, 95% CI [1.01, 3.45], p = 0.05, 95% PI [0.74, 4.10]) compared with women without pregnancy loss. There was no evidence of increased risk of cardiovascular disease (IHD: RR 1.11, 95% CI [0.98, 1.27], 95% PI [0.46, 2.76] or cerebrovascular: RR 1.01, 95% CI [0.85, 1.21]) in women experiencing a miscarriage. Only women with a previous stillbirth were more likely to develop type 2 diabetes mellitus (T2DM) (RR: 1.16, 95% CI [1.07 to 2.26]; p < 0.001, 95% PI [1.05, 1.35]). Women with a stillbirth history had an increased risk of developing renal morbidities (RR 1.97, 95% CI [1.51, 2.57], p < 0.001, 95% [1.06, 4.72]) compared with controls. Women with a history of stillbirth had lower risk of breast cancer (RR: 0.80, 95% CI [0.67, 0.96], p-0.02, 95% PI [0.72, 0.93]). There was no evidence of altered risk of other malignancies in women experiencing pregnancy loss compared to controls. There was no evidence of long-term mental illness risk in women with previous pregnancy losses (stillbirth: RR 1.90, 95% CI [0.93, 3.88], 95% PI [0.34, 9.51], miscarriage: RR 1.78, 95% CI [0.88, 3.63], 95% PI [1.13, 4.16]). The main limitations include the potential for confounding due to use of aggregated data with variable degrees of adjustment. CONCLUSIONS: Our results suggest that women with a history of stillbirth have a greater risk of future cardiovascular disease, T2DM, and renal morbidities. Women experiencing miscarriages, single or multiple, do not seem to have an altered risk.
Subject(s)
Abortion, Spontaneous , Maternal Mortality , Stillbirth , Humans , Female , Pregnancy , Abortion, Spontaneous/epidemiology , Stillbirth/epidemiology , Risk FactorsABSTRACT
Background: Feminizing genital gender affirmation surgery (fgGAS) may be an essential adjunct in the care of some transgender women and gender diverse individuals with gender incongruence. However, the comparison of different techniques of fgGAS may be confounded by variable outcome reporting and the use of inconsistent outcomes in the literature. This systematic review provides the most in-depth examination of fgGAS studies to date, and summarizes all reported outcomes, definitions, and the times when outcomes were assessed following these surgical interventions. Aims/Methods: This work intends to quantify the levels of outcome variability and definition heterogeneity in this expanding field and provides guidance on outcome reporting for future study authors. Candidate studies for this systematic review were sourced via an electronic, multi-database literature search. All primary, clinical research studies of fgGAS were included with no date limits. Paired collaborators screened each study for inclusion and performed data extraction to document the outcomes, definitions, and times of outcome assessment following fgGAS. Results: After screening 1225 studies, 93 studies proceeded to data extraction, representing 7681 patients. 2621 separate individual outcomes were reported, 857 (32.7%) were defined, and the time of outcome assessment was given for 1856 outcomes (70.8%) but relied on nonspecific ranges of follow-up dates. "Attainment of orgasm", "Neovaginal stenosis", and "Neovaginal depth/length" were among the most commonly reported outcomes. Profound heterogeneity existed in the definitions used for these and for all outcomes reported in general. Discussion: The results demonstrate a need for clear outcomes, agreed definitions, and times of outcome assessment following fgGAS in transgender women and gender diverse individuals. The adoption of a consistent set of outcomes and definitions reported by all future studies of fgGAS (a Core Outcome Set) will aid in improving treatment comparisons in this patient group. This review is the first step in that process.