Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched Pubmed and EMBASE up to August 20, 2020, to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of ICU admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RR), and 95% confidence intervals (CI) were calculated using a random-effects model. 34 adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14/34 adult studies included only hospitalized patients). The risk of death amongst adult patients was 34% (95% CI 28-39, N=3240) in this sample of predominantly hospitalized patients. Patients aged >60 years had a significantly higher risk of death than patients <60 years (RR 1.82, 95% CI 1.45-2.27, N=1169). The risk of death in pediatric patients was 4% (95% CI 1-9, N=102). The RR of death comparing patients with recent systemic anti-cancer therapy to no treatment was 1.17 (95% CI 0.83-1.64; N=736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients >60 years have significantly higher mortality, and pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

Giant condyloma acuminatum, originally described by Buschke and Loewenstein in 1925 as a lesion of the penis, is more rarely seen in the anorectum and is characterized by clinical malignancy in the face of histologic benignity; however, malignant transformation to frankly invasive squamous-cell carcinoma has been described. Malignant transformation has been reported in 15 patients with "ordinary" condylomata acuminata as well. Twenty giant condylomata acuminata have been previously reported, six of which (30 percent) went on to develop squamous-cell carcinoma. The authors report eight cases of giant condylomata acuminata with invasive squamous-cell carcinoma developing in four patients. Light and electron microscopic methods were used to verify the diagnosis of squamous-cell carcinoma and/or giant condyloma acuminatum in our cases. Human papillomavirus (HPV), known to cause condylomata acuminata, is also known to induce these tumors. The authors support the hypothesis that giant condyloma acuminatum represents an intermediate lesion in a pathologic continuum from condyloma acuminatum to squamous-cell carcinoma. These lesions have a propensity for recurrence, likelihood of malignant transformation, and significant mortality. Therefore, early and radical local excision, and in cases of recurrence, invasion, or malignant transformation, abdominoperineal resection, along with vigilant follow-up, provides the only current hope for cure.

The structure of the anal canal was examined in histology slides. Hemorrhoids are normal features of the human anatomy. They are pads that bulge into the lumen. Hemorrhoids have three parts: 1) the lining, which can be mucosa or anoderm; 2) the stroma with blood vessels, smooth muscle, and supporting connective tissue; and 3) the anchoring connective tissue system, which secures the hemorrhoids to the internal sphincter and the conjoined longitudinal coat. The anchoring and supporting connective tissue system deteriorates with aging. The hemorrhoids not only bulge, but descend into the lumen. This becomes observable in the third decade of life, with individual differences. The veins become distended as they lose their support. The descended loose lining becomes more sensitive to pressure from straining and to trauma from the stool. There can be a stasis in the veins, with clot formations and swelling, or erosions of the lining, with bleeding. The hemorrhoids become symptomatic.

Haematology patients receiving chemo-or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP). COVID-19 diagnosis coincided with a new diagnosis of a haematological malignancy in four patients. Among patients, 82% were on systemic anti-cancer therapy (SACT) at the time of COVID-19 diagnosis. Of hospitalised patients, 37% (19/51) died while all four outpatients recovered. Risk factors for severe disease or mortality were similar to those in other published cohorts. Raised C-reactive protein at diagnosis predicted an aggressive clinical course. The majority of patients recovered from COVID-19, despite receiving recent SACT. This suggests that SACT, where urgent, should be administered despite intercurrent COVID-19 infection, which should be managed according to standard pathways. Delay or modification of therapy should be considered on an individual basis. Long-term follow-up studies in larger patient cohorts are required to assess the efficacy of treatment strategies employed during the pandemic.

Key Points Allo-HSCT with RIC is safe and effective in younger adults with severe PID. Referral triggers should include severe infections, autoimmunity, malignancy, and disease progression despite conservative management.

Until recently, hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently, treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harboring integrations near oncogenes. Here, we describe a case of a presplenectomized 30-year-old patient with severe WAS manifesting as cutaneous vasculitis, inflammatory arthropathy, intermittent polyclonal lymphoproliferation, and significant chronic kidney disease and requiring long-term immunosuppressive treatment. Following reduced-intensity conditioning, there was rapid engraftment and expansion of a polyclonal pool of transgene-positive functional T cells and sustained gene marking in myeloid and B-cell lineages up to 20 months of observation. The patient was able to discontinue immunosuppression and exogenous immunoglobulin support, with improvement in vasculitic disease and proinflammatory markers. Autologous gene therapy using a lentiviral vector is a viable strategy for adult WAS patients with severe chronic disease complications and for whom an allogeneic procedure could present an unacceptable risk. This trial was registered at www.clinicaltrials.gov as #NCT01347242.

The clinical records of 835 patients were reviewed. Five hundred ninety four had symptoms of hemorrhoids (symptomatic group) and 241 had no symptoms (asymptomatic group). Eight-six per cent of the entire group had hemorrhoids, 88 per cent among the symptomatic group and 82 per cent among the asymptomatic group. It was felt that if the prevalence rate of hemorrhoids in the symptomatic and asymptomatic groups is similar or close to similar in every age, it is likely that a certain number of people will have hemorrhoids in every age group irrespective of the presence or absence of symptoms. If the prevalence rate is high, it would seem to support the theory that hemorrhoids are normal parts of the human body, not a disease but a sign of aging. Although the difference in the prevalence rate overall in the symptomatic and asymptomatic groups, 88 versus 82 per cent was mathematically significant, this was due to the large sample size and it was small enough to be without clinical importance. No significant differences in the prevalence rate between symptomatic and asymptomatic patients within age groups were found.

CD28 and CTLA-4 (CD152) play essential roles in regulating T cell immunity, balancing the activation and inhibition of T cell responses, respectively. Although both receptors share the same ligands, CD80 and CD86, the specific requirement for two distinct ligands remains obscure. In the present study, we demonstrate that, although CTLA-4 targets both CD80 and CD86 for destruction via transendocytosis, this process results in separate fates for CTLA-4 itself. In the presence of CD80, CTLA-4 remained ligand bound, and was ubiquitylated and trafficked via late endosomes and lysosomes. In contrast, in the presence of CD86, CTLA-4 detached in a pH-dependent manner and recycled back to the cell surface to permit further transendocytosis. Furthermore, we identified clinically relevant mutations that cause autoimmune disease, which selectively disrupted CD86 transendocytosis, by affecting either CTLA-4 recycling or CD86 binding. These observations provide a rationale for two distinct ligands and show that defects in CTLA-4-mediated transendocytosis of CD86 are associated with autoimmunity.