Antiretroviral Therapy and Detection of High-grade Cervical Intraepithelial Neoplasia (CIN2+) at Post-CIN Management Follow-up Among Women Living With Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

BACKGROUND: We evaluated the association of antiretroviral therapy (ART), CD4+ count and human immunodeficiency virus (HIV) plasma viral load (PVL) on high-grade cervical intraepithelial neoplasia (CIN2+) detection at follow-up after CIN management among women living with HIV (WLHIV). METHODS: Medline, Embase, Global Health, and PubMed were searched from 1 January 1996 to 15 January 2020. Eligible studies investigated the association of ART, CD4+ count, or HIV PVL on histology-confirmed CIN2+ detection at follow-up. Summary estimates were obtained using random-effects meta-analyses; heterogeneity was examined using I2 statistic. PROSPERO registration: CRD42018115631. RESULTS: Eight studies representing 9 populations were identified, including 1452 WLHIV followed between 6 and 33 months post-CIN management. Pooled data from 8 populations (n = 1408) suggested weak evidence of a decreased risk of CIN2+ detection at follow-up among ART users compared to ART-naive women (crude odds ratio [cOR] = 0.70, 95% confidence interval [CI]: .36-1.36; I2 = 64.5%, P = .006; adjusted risk ratio [aRR] from 3 studies = 0.66, 95% CI: .20-2.24; I2 = 78.7%, P = .009). A significant association was observed in high-income countries (cOR = 0.24, 95% CI: .13-.45; I2 = 0.0%, P = .77) but not in low and middle-income countries (cOR = 1.13, 95% CI: .67-1.92; I2 = 18.8%, P = .30).In 3 populations, ART users with HIV PVL <50 copies/ml were less likely to have CIN2+ detection at follow-up (vs ≥50 copies/mL: cOR = 0.55, 95% CI: .32-.94; I2 = 0.0%, P = .23).There was weak evidence of decreased CIN2+ detection at follow-up among WLHIV with higher contemporary CD4+ cell counts (≥200 cells/µL vs <200 cells/µL [cOR = 0.36, 95% CI: .04-3.13; I2 = 81.3%, P = .021]) and significant evidence among women with a higher nadir CD4+ count (≥350 cells/µl vs <200 cells/µl [adjusted hazard ratio [aHR] = 0.35, 95% CI: .15-.84; I2 = 0%, P = .64]). CONCLUSION: ART may reduce the risk of CIN2+ detection at follow-up; this effect is most likely enhanced by a combination of adequate HIV control and excisional CIN treatment. Our findings support recommendations of early ART and the integration of CIN2+ screening and management into HIV care.

Antibody responses to the full-length VAR2CSA and its DBL domains in Cameroonian children and teenagers.

BACKGROUND: Antigenic variation of Plasmodium falciparum erythrocyte membrane protein 1 is a key parasite mechanism for immune evasion and parasite survival. It is assumed that the number of parasites expressing the same var gene must reach high enough numbers before the host can produce detectable levels of antibodies (Ab) to the variant. VAR2CSA is a protein coded for by one of 60 var genes that is expressed on the surface of infected erythrocytes (IE) and mediates IE binding to the placenta. The idea that Ab to VAR2CSA are pregnancy-associated was challenged when VAR2CSA-specific Ab were reported in children and men. However, the frequency and conditions under which Ab to VAR2CSA are produced outside pregnancy is unclear. This study sought to determine frequency, specificity and level of Ab to VAR2CSA produced in children and whether children with hyperparasitaemia and severe malaria are more likely to produce Ab to VAR2CSA compared to healthy children. METHODS: Antibody responses to a panel of recombinant proteins consisting of multiple VAR2CSA Duffy-binding-like domains (DBL) and full-length VAR2CSA (FV2) were characterized in 193 1-15 year old children from rural Cameroonian villages and 160 children with severe malaria from the city. RESULTS: Low Ab levels to VAR2CSA were detected in children; however, Ab levels to FV2 in teenagers were rare. Children preferentially recognized DBL2 (56-70%) and DBL4 (50-60%), while multigravidae produced high levels of IgG to DBL3, DBL5 and FV2. Sixty-seven percent of teenage girls (n = 16/24) recognized ID1-ID2a region of VAR2CSA. Children with severe forms of malaria had significantly higher IgG to merozoite antigens (all p < 0.05), but not to VAR2CSA (all p > 0.05) when compared to the healthy children. CONCLUSION: The study suggests that children, including teenage girls acquire Ab to VAR2CSA domains and FV2, but Ab levels are much lower than those needed to protect women from placental infections and repertoire of Ab responses to DBL domains is different from those in pregnant women. Interestingly, children with severe malaria did not have higher Ab levels to VAR2CSA compared to healthy children.

A Case of Milk-Alkali Syndrome.

Milk-alkali syndrome is described by a triad of elevated levels of calcium, metabolic alkalosis, and acute kidney injury that historically occurred as a result of the combined intake of large amounts of calcium and absorbable alkali. It is becoming common recently with the use of over-the-counter calcium supplements for osteoporosis treatment in postmenopausal women. We present a case of a 62-year-old female who presented with generalized weakness. She was noted to have severe hypercalcemia, and impaired renal function with a significant history of daily over-the-counter calcium supplement use and as-needed calcium carbonate use for gastroesophageal reflux disease (GERD). This case highlights the stepwise approach to the evaluation and management of hypercalcemia. She was appropriately treated with the resolution of hypercalcemia and presenting symptoms.

A Case of Massive Lower Gastrointestinal Bleed from a Cystic Artery Pseudoaneurysm Bleeding through a Cholecystocolic Fistula.

BACKGROUND Acute lower gastrointestinal bleeding (GIB) is often associated with favorable outcomes. It is readily diagnosed and managed with colonoscopy, or may resolve spontaneously. Rarely, extra-colonic sources of bleeding may masquerade as lower GIB, posing a diagnostic challenge and potentially lead to harm if there are therapeutic delays. An example is cystic artery pseudoaneurysm, a rare complication of acute cholecystitis and laparoscopic cholecystectomy, which may bleed through a cholecystocolic fistula presenting as lower GIB. CASE REPORT A 66-year-old man with multiple comorbidities including coronary artery disease with multiple stents and peripheral arterial disease presented with massive hematochezia. He was on aspirin 81 mg, clopidogrel 75 mg, and rivaroxaban 20 mg daily. The patient was hemodynamically unstable with BP 77/50 mmHg and heart rate 115 beats/min. Pertinent laboratory investigations showed hemoglobin 10.4 g/dL, WBC 17.2×10³/uL, platelet 437×10³/uL, and INR 1.28. Total bilirubin and liver enzymes were normal. Following prompt volume resuscitation with crystalloids and 2 units of O-negative blood, CT angiogram of the abdomen revealed a ruptured cystic artery pseudoaneurysm bleeding through a cholecystocolic fistula. This developed as a complication of undiagnosed gangrenous cholecystitis. The patient was sent for transcatheter embolization and the bleeding was controlled. The gangrenous cholecystitis was managed conservatively due to the patient's high surgical risk. CONCLUSIONS Although extra-intestinal sources of gastrointestinal bleeding are rare, clinicians should maintain a high index of suspicion, especially in elderly patients presenting concomitantly with right upper-quadrant pain. As delayed diagnosis leads to increased fatality rates, a prompt CT angiogram of the abdomen is pertinent in suspected cases.