A Rare Report of the Coexistence of Sickle Cell Disease, Neurofibromatosis Type 1, and Intracranial Hypertension in a Pediatric Patient.

A pediatric female with sickle cell disease (SCD) and neurofibromatosis type 1 was noted to have incidental papilledema, with subsequent workup showing an elevated opening pressure. She was diagnosed with intracranial hypertension and began treatment with acetazolamide. Hydroxyurea was also discontinued. Acetazolamide was tapered off, and hydroxyurea was restarted with no worsening in her ophthalmologic exam. We report this case due to the rare occurrence of all 3 conditions, and while intracranial hypertension has been reported in SCD, the diagnostic workup for papilledema in hemoglobinopathies is not well defined. This case helps delineate the presentation and diagnostic workup of papilledema in SCD.

Hidradenitis Suppurativa in the United States: Insights From the National Inpatient Sample (2008-2017) on Contemporary Trends in Demographics, Hospitalization Rates, Chronic Comorbid Conditions, and Mortality.

Background Hidradenitis suppurativa (HS) is a clinical condition characterized by the formation of painful lumps under the skin. It often affects intertriginous areas like armpits and groin. There is a paucity of contemporary data on patient and hospital-level characteristics of HS in the United States. Methods We analyzed the Nationwide Inpatient Sample (NIS) for retrospective analysis to calculate the frequency and yearly rates of HS hospitalizations, demographic variations, rates of comorbidities, and length of stay. Results The rate of hospitalizations with HS as a primary diagnosis increased from 7.9 per 100,000 all-cause hospitalizations in 2008 to 11.6 per 100,000 all-cause hospitalizations in 2017 (p < 0.0001). The mean age ± standard error of hospitalized patients was 39.5 ± 0.2 years. The age group of 18-34 years was the most affected. Women showed a higher preponderance of the disease than men (56.6% vs. 43.5%, p < 0.0001). The Black race was the most affected out of all the racial groups (59.9%). Most hospitalizations were in large, urban teaching hospitals. Hypertension (34.9%), skin and subcutaneous tissue infections (26.5%), and diabetes mellitus (25.9%) were the most common comorbidities. Out of the total hospitalizations with HS, 12.7% were found to have a major or extreme loss of function and 3.5% were at a major or extreme likelihood of dying. Conclusions HS disproportionately affects young adults, women, and Black patients. A significant proportion of these patients are at a major risk of major loss of bodily function or death. Prospective studies are needed to identify the risk factors for hospitalizations in these patient populations and devise appropriate prevention and treatment strategies.

Association of Sociodemographic Factors With Immunotherapy Receipt for Metastatic Melanoma in the US.

Importance: Strides to improve survival in metastatic melanoma have been made with the use of immunotherapeutic agents in the form of immune checkpoint inhibitors. Objective: To examine the factors associated with immunotherapy receipt in patients with metastatic melanoma in the era of immune checkpoint inhibitors and the Patient Protection and Affordable Care Act. Design, Setting, and Participants: This cohort study used data on 9882 patients with metastatic melanoma diagnosed from January 1, 2013, to December 31, 2016, from the National Cancer Database. Patients who did not have documentation regarding immunotherapy receipt were excluded. Data analysis was performed from July 1, 2019, to December 15, 2019. Exposure: Receipt of immunotherapy. Main Outcomes and Measures: The primary outcome was the association of receipt of immunotherapy as first-line therapy with sociodemographic factors. The secondary outcome was overall survival by receipt of immunotherapy. Results: A total of 9512 patients (mean [SD] age, 65.1 [14.4] years; 6481 [68.1%] male; 9217 [96.9%] White) met the criteria for treatment analysis. A total of 3428 (36.0%) received immunotherapy, and 6084 (64.0%) did not. Increasing age (odds ratio [OR], 0.98; 95% CI, 0.97-0.98; P < .001) and increasing Charlson-Deyo comorbidity index (OR, 0.86; 95% CI, 0.80-0.92; P < .001) were associated with lower odds of receiving immunotherapy on regression analysis. Diagnosis in Medicaid expansion states (OR, 1.16; 95% CI, 1.05-1.27; P = .003), treatment at an academic or integrated cancer network program (OR, 1.59; 95% CI, 1.45-1.75; P < .001), and residence within the highest quartile of high school graduation rate zip code area (OR, 1.31; 95% CI, 1.09-1.56; P = .003) were associated with an increased likelihood of receiving immunotherapy. Median overall survival was 10.1 months (95% CI, 9.6-10.6 months) among all patients. Patients who received first-line immunotherapy had a median overall survival of 18.4 months (95% CI, 16.6-20.1 months) compared with 7.5 months (95% CI, 7.0-7.9 months) (P < .001) among patients who did not. Conclusions and Relevance: In this cohort study, patients who received immunotherapy for metastatic melanoma had improved overall survival. Residence in Medicaid expansion states, younger age, low comorbidity index, care at academic medical centers or integrated network cancer programs, and residence in zip codes within the highest quartile of high school graduation were associated with an increased likelihood of receiving immunotherapy. Recognizing sociodemographic associations with treatment receipt is important to identify potential barriers to treatment.

Reactivity of Routine HIV Antibody Tests in Children With Perinatally Acquired HIV-1 in England: Cross-sectional Analysis.

We assessed HIV antibody prevalence in children with perinatally acquired HIV in England. Eighteen percent (10/55) of those starting combination antiretroviral therapy <6 months of age were seronegative at median age 9.1 years and had lower viral load at diagnosis and combination antiretroviral therapy start and fewer viral rebounds, than 45 of 55 seropositives. Implications for patient selection for HIV cure research, and interpretation of routine antibody testing, are discussed.

Pre-clinical development of gene modification of haematopoietic stem cells with chimeric antigen receptors for cancer immunotherapy.

Patients with refractory or recurrent B-lineage hematologic malignancies have less than 50% of chance of cure despite intensive therapy and innovative approaches are needed. We hypothesize that gene modification of haematopoietic stem cells (HSC) with an anti-CD19 chimeric antigen receptor (CAR) will produce a multi-lineage, persistent immunotherapy against B-lineage malignancies that can be controlled by the HSVsr39TK suicide gene. High-titer third-generation self-inactivating lentiviral constructs were developed to deliver a second-generation CD19-specific CAR and the herpes simplex virus thymidine kinase HSVsr39TK to provide a suicide gene to allow ablation of gene-modified cells if necessary. Human HSC were transduced with such lentiviral vectors and evaluated for function of both CAR and HSVsr39TK. Satisfactory transduction efficiency was achieved; the addition of the suicide gene did not impair CAR expression or antigen-specific cytotoxicity, and determined marked cytotoxicity to ganciclovir. NSG mice transplanted with gene-modified human HSC showed CAR expression not significantly different between transduced cells with or without HSVsr39TK, and expression of anti-CD19 CAR conferred anti-tumor survival advantage. Treatment with ganciclovir led to significant ablation of gene-modified cells in mouse tissues. Haematopoietic stem cell transplantation is frequently part of the standard of care for patients with relapsed and refractory B cell malignancies; following HSC collection, a portion of the cells could be modified to express the CD19-specific CAR and give rise to a persistent, multi-cell lineage, HLA-independent immunotherapy, enhancing the graft-versus-malignancy activity.

The management of HIV in pregnancy: A 10-year experience.

OBJECTIVE: The package of care to reduce HIV mother to child transmission (MTCT) has evolved significantly since trials of ante and intrapartum antiretroviral therapy (ART) in 1994. In the UK MTCT rate has fallen from 25.6% in the 1990s to 0.46%. We review the management of HIV in pregnancy in Brighton in the context of evolving guidelines. STUDY DESIGN: HIV, obstetric and neonatal notes of all HIV positive women, pregnant between 2003 and 2014, were reviewed. RESULTS: 97 pregnancies in 75 women were identified, resulting in 79 live births. Antenatal HIV diagnosis was made in 22 (28%). The proportion of pregnancies in those with known HIV at conception increased over the time period. At conception 58 (60%) were on ART, 33 (57%) of who continued on their original regimen. 34 (35%) initiated ART following conception: 14 known to be HIV positive, 20 diagnosed during pregnancy. Two did not start ART (1 due to miscarriage, 1 as diagnosed post-delivery) and in three cases ART history was unavailable due to transfer to alternative centres. ART was initiated on average at 22 weeks gestation (range 6-34). 4(5%) received Zidovudine (AZT) monotherapy, all before 2006. Choice of combination ART (cART) varied with time reflecting changing guidelines. Prior to 2008 an AZT containing regimen was used in 83% versus 8% after. Planned mode of delivery was documented in 73: 30(41%) planned a normal vaginal delivery (NVD), 43(59%) a caesarean section (CS). The viral load (VL) was <50copies/mL in 58(76%) at 36 weeks and 64(84%) at delivery. 90% with a detectable VL at 36 weeks delivered via CS. 100% received neonatal post-exposure prophylaxis (PEP): 68(88%) AZT monotherapy, 9(12%) cART. 84% initiated PEP within four hours. 90% completed 28days. 8(10%) babies experienced side effects. In the 10-year review period, one infant (1.3%) was diagnosed HIV positive. Both mother and infant received care in accordance with guidelines, including neonatal PEP within 4hours. CONCLUSION: Care of the HIV positive pregnant woman in Brighton has been successful with overall transmission consistent with that seen nationally. Despite effective preventative strategies MTCT remains a risk and women should be counselled accordingly.