Kaposi’s sarcoma is an angioproliferative tumor caused by human herpesvirus 8 in the context of immunodeficiency, such as that induced by HIV infection or immunosuppressive therapy. Its incidence has ...dramatically fallen in patients living with HIV (PLHIV) since the introduction of potent antiretroviral combinations 25 years ago due to the restoration of immunity and better control of HIV replication. However, KS is still one of the most frequently occurring cancers in PLHIV, in particular in men who have sex with men and in sub-Saharan Africa, where it is still endemic. Even in the context of restored immunity, the risk of KS is still more than 30 times higher in PLHIV than in the general population. Recent evidence indicates that early initiation of antiretroviral treatment, which is recommended by current guidelines, may reduce the risk of KS but it needs to be accompanied by early access to care. This review mainly focuses on the recent epidemiological features of KS in the context of HIV infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Confessions are uncommon in abusive head trauma (AHT) cases, and there is debate over whether shaking alone can cause the injuries characteristic of AHT. The objective of this article is to correlate ...legal statements by perpetrators with medical documentation to offer insights into the mechanism of injury.
In this retrospective observational study we examined forensic evidence from 112 cases referred for AHT over a 7-year period. We compared 29 cases in which a perpetrator confessed to violence toward the child with 83 cases in which there was no confession. Inclusion criteria were subdural hematoma (SDH) on computed tomography and perpetrator admission of a causal relationship between the violence inflicted and the child's symptoms. Groups were compared by using Student's t test for age and Fisher's exact test for gender, death, fractures, retinal hemorrhages, ecchymoses, symptoms, and SDH patterns. All medical records from birth to diagnosis, imaging studies, and written investigation reports were reviewed.
All confessions came from forensic investigations. There was no statistically significant difference between the 2 groups for any of the variables studied. Shaking was described as extremely violent (100%) and was repeated (55%) from 2 to 30 times (mean: 10) because it stopped the infant's crying (62.5%). Impact was uncommon (24%). No correlation was found between repeated shaking and SDH densities.
This unique forensic case series confirms the violence of shaking. The high frequency of habitual AHT is a strong argument for reporting suspected cases to judicial authorities and helps to explain the difficulty in dating the injuries.
Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost ...importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013.
We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 comparator, 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART.
88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men.
Even in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements.
UK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.
Patients with hematological malignancy and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatments impair humoral ...response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancy and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n = 81) or not (n = 120) with CCP between May 1, 2020 and April 1, 2021. The overall survival of the whole cohort was 65% (95% CI = 56-74.9) and 77.5% (95% CI = 68.5-87.7) for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20-exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI = 31-80) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To study recent trends in the incidence of anal cancer in HIV-infected patients receiving long-term combined antiretroviral treatment (cART) compared with the general population.
From the French ...Hospital Database on HIV, we identified 263 cases of invasive anal squamous cell carcinoma confirmed histologically between 1992 and 2008. We compared incidence rates of anal cancer across four calendar periods: 1992-1996 (pre-cART period), 1997-2000 (early cART period), and 2001-2004 and 2005-2008 (recent cART periods). Standardized incidence ratios (SIRs) were calculated by using general population incidence data from the French Network of Cancer Registries.
In HIV-infected patients, the hazard ratio (HR) in the cART periods versus the pre-cART period was 2.5 (95% CI, 1.28 to 4.98). No difference was observed across the cART calendar periods (HR, 0.9; 95% CI, 0.6 to 1.3). In 2005-2008, HIV-infected patients compared with the general population had an excess risk of anal cancer, with SIRs of 109.8 (95% CI, 84.6 to 140.3), 49.2 (95% CI, 33.2 to 70.3), and 13.1 (95% CI, 6.8 to 22.8) for men who have sex with men (MSM), other men, and women, respectively. Among patients with CD4 cell counts above 500/μL for at least 2 years, SIRs were 67.5 (95% CI, 41.2 to 104.3) when the CD4 nadir was less than 200/μL for more than 2 years and 24.5 (95% CI, 17.1 to 34.1) when the CD4 nadir was more than 200/μL.
Relative to that in the general population, the risk of anal cancer in HIV-infected patients is still extremely high, even in patients with high current CD4 cell counts. cART appears to have no preventive effect on anal cancer, particularly in MSM.
We studied the frequency and risk factors for loss of long-term non-progressor (LTNP) and HIV controller (HIC) status among patients identified as such in 2005 in the French Hospital Database on HIV ...(FHDH-ANRS CO4).
We selected patients who were treatment-naïve and asymptomatic in 2005 (baseline). Those with ≥8 years of known HIV infection and a CD4 cell nadir ≥500/mm3 were classified as LTNP and those with ≥10 years of known HIV infection and 90% of plasma viral load (VL) values ≤500 copies/ml in the absence of cART as HIC. cART initiation without loss of status and death from non AIDS-defining causes were considered as competing events.
After 5 years of follow-up, 33% (95%CI; 27-42) of 171 LTNP patients and 17% (95%CI; 10-30) of 72 HIC patients had lost their status. In multivariable analyses, loss of LTNP status was associated with lower baseline CD4 cell counts and CD4/CD8 ratios. Only VL was significantly associated with loss of HIC status after adjustment for the baseline CD4 cell count, the CD4/CD8 ratio, and concomitant LTNP status. The hazard ratio for loss of HIC status was 5.5 (95%CI, 1.5-20.1) for baseline VL 50-500 vs ≤50 cp/mL, after adjustment for the baseline CD4 cell count.
One-third of LTNP and one-fifth of HIC patients lost their status after 5 years of follow-up, raising questions as to the possible benefits and timing of ART initiation in these populations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: The “complex of myxomas, spotty skin pigmentation, and endocrine overactivity,” or “Carney complex” (CNC), is caused by inactivating mutations of the regulatory subunit type 1A of the ...cAMP-dependent protein kinase (PRKAR1A) gene and as yet unknown defect(s) in other gene(s). Delineation of a genotype-phenotype correlation for CNC patients is essential for understanding PRKAR1A function and providing counseling and preventive care.
Methods: A transatlantic consortium studied the molecular genotype and clinical phenotype of 353 patients (221 females and 132 males, age 34 ± 19 yr) who carried a germline PRKAR1A mutation or were diagnosed with CNC and/or primary pigmented nodular adrenocortical disease.
Results: A total of 258 patients (73%) carried 80 different PRKAR1A mutations; 114 (62%) of the index cases had a PRKAR1A mutation. Most PRKAR1A mutations (82%) led to lack of detectable mutant protein (nonexpressed mutations) because of nonsense mRNA mediated decay. Patients with a PRKAR1A mutation were more likely to have pigmented skin lesions, myxomas, and thyroid and gonadal tumors; they also presented earlier with these tumors. Primary pigmented nodular adrenocortical disease occurred earlier, was more frequent in females, and was the only manifestation of CNC with a gender predilection. Mutations located in exons were more often associated with acromegaly, myxomas, lentigines, and schwannomas, whereas the frequent c.491-492delTG mutation was commonly associated with lentigines, cardiac myxomas, and thyroid tumors. Overall, nonexpressed PRKAR1A mutations were associated with less severe disease.
Conclusion: CNC is genetically and clinically heterogeneous. Certain tumors are more frequent, with specific mutations providing some genotype-phenotype correlation for PRKAR1A mutations.
Carney complex is genetically and clinically heterogeneous. Certain tumors are more frequent with specific mutations providing some genotype-phenotype correlation for PRKAR1A mutations.
To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years.
We used data from 18 ...European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA.
During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years.
Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 ...with Spectrum's estimates.
The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts.
In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates.
Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.
Background:
Percutaneous transhepatic biliary drainage (PTBD) is widely performed as a salvage procedure in patients with unresectable malignant obstruction of the common bile duct (CBD) after failed ...endoscopic retrograde cholangiopancreatography (ERCP) or in case of surgically altered anatomy. Endoscopic ultrasound-guided hepaticogastrostomy (EU-HGS) is a more recently introduced alternative to relieve malignant obstructive jaundice. The aim of this prospective observational study was to compare the outcome, efficacy and adverse events of EU-HGS and PTBD.
Methods:
From April 2012 to August 2015, consecutive patients with malignant CBD obstruction who underwent EU-HGS or PTBD in two tertiary-care referral centers were included. The primary endpoint was the clinical success rate. Secondary endpoints were technical success, overall survival, procedure-related adverse events, incidence of adverse events, and reintervention rate.
Results:
A total of 51 patients (EU-HGS, n = 31; PTBD, n = 20) were included. Median survival was 71 days (range 25–75th percentile; 30–95) for the EU-HGS group and 78 days (range 25–75th percentile; 42–108) for the PTBD group (p = 0.99). Technical success was achieved in all patients in both groups. Clinical success was achieved in 25 (86%) of 31 patients in the EU-HGS group and in 15 (83%) of 20 patients in the PTBD group (p = 0.88). There was no difference in adverse events rates between the two groups (EU-HGS: 16%; PTBD: 10%) (p = 0.69). Four deaths within 1 month (two hemorrhagic and two septic) were considered procedure related (two in the EU-HGS group and two in the PTBD group). Overall reintervention rate was significantly lower after EU-HGS (n = 2) than after PTBD (n = 21) (p = 0.0001). Length of hospital stay was shorter after EU-HGS (8 days versus 15 days; p = 0.002).
Conclusions:
EU-HGS can be an effective and safe mini invasive-procedure alternative to PTBD, with similar success and adverse-event rates, but with lower rates of reintervention and length of hospitalization.
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