The COVID-19 pandemic's impact on worry and medical disruptions reported by individuals with chromosome 22q11.2 copy number variants and their caregivers.

BACKGROUND: The world has suffered immeasurably during the COVID-19 pandemic. Increased distress and mental and medical health concerns are collateral consequences to the disease itself. The Genes to Mental Health (G2MH) Network consortium sought to understand how individuals affected by the rare copy number variations of 22q11.2 deletion and duplication syndrome, associated with neurodevelopmental/neuropsychiatric conditions, were coping. The article focuses on worry and disruptions in medical care caused by the pandemic. METHODS: The University of Pennsylvania COVID-19 Stressor List and care disruption questions were circulated by 22 advocacy groups in English and 11 other languages. RESULTS: A total of 512 people from 23 countries completed the survey; most were caregivers of affected individuals. Worry about family members acquiring COVID-19 had the highest average endorsed worry, whilst currently having COVID-19 had the lowest rated worry. Total COVID-19 worries were higher in individuals completing the survey towards the end of the study (later pandemic wave); 36% (n = 186) of the sample reported a significant effect on health due to care interruption during the pandemic; 44% of individuals (n = 111) receiving care for their genetic syndrome in a hospital setting reported delaying appointments due to COVID-19 fears; 12% (n = 59) of the sample reported disruptions to treatments; and of those reporting no current disruptions, 59% (n = 269) worried about future disruptions if the pandemic continued. Higher levels of care disruptions were related to higher COVID-19 worries (Ps < 0.005). Minimal differences by respondent type or copy number variation type emerged. CONCLUSIONS: Widespread medical care disruptions and pandemic-related worries were reported by individuals with 22q11.2 syndrome and their family members. Reported worries were broadly consistent with research results from prior reports in the general population. The long-term effects of COVID-19 worries, interruptions to care and hospital avoidance require further study.

Comparative performance of the Biocentric Generic Viral Load, Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and m2000 Abbott assays for quantifying HIV-1 B and non-B strains: Underestimation of some CRF02 strains.

BACKGROUND: HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART). OBJECTIVES: The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France. STUDY DESIGN: The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and Abbott m2000 RealTime HIV-1 assays. A total of 1885 HIV-1 plasma samples were tested, including 684 samples from patients included in the ANRS-Primo Cohort. RESULTS: We found a good concordance of quantification between the Roche v2.0 and the Biocentric assays, both of which were superior to the Roche v1.5 assay. We show moderate agreement between techniques; however, CRF02_AG strains and undetermined viruses were underestimated when quantified with the Roche CAP/CTM v2.0. In contrast, a comparison of the Biocentric and Abbott assay results showed strong agreement between assays, indicating that both are well suited for quantification of CRF02_AG strains. Moreover, a 2% underestimation of the B subtypes was observed with the Biocentric assay. CONCLUSIONS: These results have implications for viral load monitoring in Western Africa, where CRF02_AG strains are highly prevalent. Closer epidemiological surveillance and evaluation of commercial assays are still necessary to better evaluate the impact of the genetic evolution of circulating viruses on HIV-RNA quantification in the regions most affected by the HIV-1 epidemic.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22-/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

The radiologic work-up in thyroid surgery: fine-needle biopsy versus scintigraphy and ultrasound.

To compare the effectiveness and predictive value of radiologic studies with fine-needle aspiration biopsy (FNAB) in correctly diagnosing thyroid lesions, we reviewed the medical records of 441 patients who had been treated surgically for thyroid disease from 1987 through 1999. We compared the results of thyroid scintigraphy, ultrasound, and FNAB with findings on final surgical pathology. The data were analyzed according to the chi-squared (chi 2) test. Of 189 thyroid scintigraphy scans that showed a hypofunctional (cold) nodule, 52 (27.5%) were found to be cancerous, and of 35 hyperfunctional (hot) nodules, two (5.7%) were malignant (sensitivity = 91%; specificity = 19%; accuracy = 38%; chi 2 = 7.67; p = 0.006). Of 66 ultrasounds that detected a solid or a mixed solid-cystic mass, 16(24.2%) were cancerous, while none of the eight sonograms that showed a purely cystic lesion was malignant (sensitivity = 100%; specificity = 14%; accuracy = 32%; chi 2 = 2.47; p = 0.116 [not statistically significant]). Of the 119 patients whose FNABs were diagnostic, 55 biopsies revealed follicular cells. Of the remaining 64 biopsies, cancer was correctly predicted in 35 of 44 patients (79.5%) and benign disease was correctly diagnosed in 18 of 20 patients (90.0%) (sensitivity = 95%; specificity = 67%; accuracy = 83%; chi 2 = 27.3; p = 0.00). We conclude that in the evaluation of thyroid lesions, FNAB is superior to imaging studies, which yield a relatively high rate of false-positive results.

No increased human herpesvirus 8 seroprevalence in patients with HIV-associated non-Hodgkin's lymphoma.

Human herpesvirus 8 (HHV-8) is closely associated with Kaposi's sarcoma (KS), HIV-associated Castleman's disease, and primary effusion lymphoma. As a high frequency of non-Hodgkin's lymphoma (NHL) has been reported in patients with HIV-associated KS, we hypothesized that HHV-8 infection could be indirectly implicated in the pathogenesis of NHL. We assessed the prevalence of HHV-8 antibodies in 63 patients with NHL compared with 126 HIV-infected matched control patients without NHL. Serum samples from cases and controls were assayed for antibodies to HHV-8 lytic and latent antigens using an indirect immunofluorescence assay. In patients with concordant serologic results, HHV-8 antibodies were detected in 41.5% of the NHL cases and 37% of the controls. This absence of a significant difference in HHV-8 seroprevalence between cases and controls (p =.73) does not support a possible role for HHV-8 infection in the development of NHL in HIV-infected patients.

The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells.

To characterize the differentiation events that selectively target insulin-producing cells to interleukin (IL)-1beta-induced apoptosis, we studied IL-1beta signaling via mitogen-activated protein kinase (MAPK) and stress-activated protein kinase in 2 pancreatic endocrine cell lines. We studied the glucagon-secreting AN-glu cell line and the insulin and the islet amyloid polypeptide-producing beta-cell line (AN-ins cells), which is derived by stable transfection of AN-glu cells with the transcription factor pancreatic duodenal homeobox factor-1. AN-ins cells were more sensitive to the cytotoxic action of IL-1beta. This increased sensitivity was not associated with a more pronounced IL-l-induced nitric oxide production in AN-ins cells, but it correlated with a more marked activation of the 3 MAPKs extracellular signal-regulated kinases (ERKs)-1/2, c-Jun NH2-terminal kinase (JNK), and p38 MAPK (p38). This led to increased phosphorylation of the transcription factors c-Jun, Elk-1, and ATF2 and of heat shock protein 25. Inhibition of ERK-1/2 and p38 did not prevent but aggravated IL-1beta-induced cell death. In contrast, inhibition of JNK by transfection with the dominant negative inhibitor of the JNK-binding domain prevented apoptosis in both cell types. Cell death could be elicited by overexpressing the catalytic domain of MAPK kinase kinase 1, a specific activator of JNK and nuclear factor-kappaB, which does not recruit ERK-1/2 or p38. Coactivation of ERK-1/2 with JNK did not prevent apoptosis. In conclusion, increased MAPK signaling in response to IL-1beta may represent a novel molecular marker of beta-cell differentiation. JNK inhibition represents an effective means of preventing IL-1beta-activated beta-cell destruction.

High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients.

Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin-6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with human herpesvirus 8 (HHV8) infection. In a prospective study of 23 HIV-infected patients with MCD, clinical symptoms of MCD were present at 45 visits, whereas patients were in chemotherapy-induced clinical remission at 50 visits. Symptoms were associated with a high level of serum C reactive protein, high HHV8 viral load in peripheral blood mononuclear cells, and high plasma human IL-6 and IL-10 levels. Strong correlations between plasma IL-6 and plasma IL-10 with the HHV8 viral load suggest that both cytokines may be involved in the pathogenesis of this virus-associated lymphoproliferative disorder.

[Cysticercosis in Guadeloupe]. / Cysticercoses en Guadeloupe.

We report two cases of cysticercosis proved by histology, one in the brain, the other in the orbit. The first case was observed in a traveller, heavy smoker, serologically negative to cysticercosis in whom an isolated cerebral tumoral metastasis was suspected and resected. The lesion was centered by a typical cysticercus of Taenia solium. The second was a periorbital intramuscular nodule observed in a child who had never left our island. The fibroinflammatory nodule was centered by a cysticercus with a scolex without rostellum and without suckers. Its histological aspect led us to the diagnosis of cysticercosis. Three species of Taenia are discussed : T. solium, T. crassiceps and T. bovis. This case shows that the human transmission of the disease may exist in Guadeloupe.

Endoscopic optic nerve decompression for traumatic blindness.

OBJECTIVES: The goal of this study was to compare the outcome of patients with traumatic optic neuropathy (TON) treated with high-dose steroids with the outcome of patients with TON treated with endoscopic optic nerve decompression (EOND) after failing high-dose steroid treatment. METHODS: During this retrospective review of patients with TON seen from 1994 to 1998, all patients were first treated with megadose methylprednisolone for 48 hours. Patients with no improvement or with worsening visual acuity were offered EOND. RESULTS: Eleven of 34 (32%) patients treated with high-dose steroids showed improvement, and 23 (68%) did not. Seventeen of the 23 patients without improvement after high-dose steroid treatment underwent EOND. Fourteen of 17 (82%) surgically treated patients had improved visual acuity, and 3 (18%) did not, with an overall improvement in 25 of 34 (74%) patients (chi(2) = 11. 338, P = 0.0007). CONCLUSION: EOND is an appropriate treatment technique for patients with TON in whom high-dose steroid treatment has failed.

Myxomas of the head and neck.

PURPOSE: Myxomas are rare, locally infiltrative, benign, connective tissue tumors that are found in bone and somatic soft tissues. This article reports our experience with head and neck myxomas and provides a comprehensive literature review. MATERIALS AND METHODS: Retrospective record review of head and neck myxoma cases seen at 2 tertiary referral centers in Houston, Texas, from 1970 to 1994. Comprehensive literature review and compilation of all myxomas reported in the head and neck. RESULTS: We identified 7 cases of true head and neck myxoma treated in our centers and identified 169 cases reported in the literature. Most often, myxomas originated in bone (mandible or maxilla) and were most commonly found in adults. All tumors except 1 were treated surgically. Recurrence rates were 6% for local or wide excision and 28% for more conservative surgery such as enucleation or curretage. CONCLUSIONS: Myxomas of the head and neck should be treated with complete excision of the tumor with clear margins.

Calcifying fibrous pseudotumor of the neck.

Calcifying fibrous pseudotumor is a rare lesion of uncertain histogenesis that has a unique histologic appearance. We report herein a case of a 24-year-old woman with a mass on the right posterior side of the neck. Magnetic resonance imaging with contrast showed a well-circumscribed mass between the right splenius and semispinalis cervicis muscles; the study suggested high collagen content. Simple excision was performed. The histologic findings were diagnostic of calcifying fibrous pseudotumor. Our review of 19 previously reported cases suggests that a good outcome is expected when a diagnosis of calcifying fibrous pseudotumor is made.

The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes.

Type 2 diabetes is a polygenic and genetically heterogeneous disease . The age of onset of the disease is usually late and environmental factors may be required to induce the complete diabetic phenotype. Susceptibility genes for diabetes have not yet been identified. Islet-brain-1 (IB1, encoded by MAPK8IP1), a novel DNA-binding transactivator of the glucose transporter GLUT2 (encoded by SLC2A2), is the homologue of the c-Jun amino-terminal kinase-interacting protein-1 (JIP-1; refs 2-5). We evaluated the role of IBi in beta-cells by expression of a MAPK8IP1 antisense RNA in a stable insulinoma beta-cell line. A 38% decrease in IB1 protein content resulted in a 49% and a 41% reduction in SLC2A2 and INS (encoding insulin) mRNA expression, respectively. In addition, we detected MAPK8IP1 transcripts and IBi protein in human pancreatic islets. These data establish MAPK8IP1 as a candidate gene for human diabetes. Sibpair analyses performed on i49 multiplex French families with type 2 diabetes excluded MAPK8IP1 as a major diabetogenic locus. We did, however, identify in one family a missense mutation located in the coding region of MAPK8IP1 (559N) that segregated with diabetes. In vitro, this mutation was associated with an inability of IB1 to prevent apoptosis induced by MAPK/ERK kinase kinase 1 (MEKK1) and a reduced ability to counteract the inhibitory action of the activated c-JUN amino-terminal kinase (JNK) pathway on INS transcriptional activity. Identification of this novel non-maturity onset diabetes of the young (MODY) form of diabetes demonstrates that IB1 is a key regulator of 3-cell function.

Parathyroid adenomas: is bilateral neck exploration necessary?

PURPOSE: The traditional surgical treatment for primary hyperparathyroidism is bilateral neck exploration with identification of all parathyroid glands. Multiple investigators who recommend initial unilateral neck exploration based on more advanced localization studies have recently challenged this approach. We reviewed our experience with primary hyperparathyroidism to determine if localization study-aided unilateral neck exploration is sufficient for a cure. MATERIALS AND METHODS: Retrospective chart review of patients with primary hyperparathyroidism. RESULTS: Sixty-eight patients underwent surgery for primary hyperparathyroidism. Forty-four patients were treated with localization study-aided unilateral neck exploration, and 24 patients were treated with bilateral neck exploration without preoperative localization studies. The most successful preoperative localization study was the technetium 99m sestamibi (T99mS) scan which correctly identified the location of adenomas in all cases in which it was used (n = 15). All patients were treated with unilateral neck exploration and were cured. This success was matched only by surgical exploration (n = 24). CONCLUSION: Unilateral neck exploration based on the results of a T99mS scan can be used as an initial approach for primary hyperparathyroidism if the scan identifies a solitary lesion. The second gland on the same side of the lesion should be biopsied, and if it is normal, the opposite side of the neck may be left undisturbed. If the second gland is not normal, or if the T99mS scan shows multiple lesions, bilateral neck exploration should be performed.

Pre-operative and per-operative factors conditioning long-term facial nerve function in vestibular schwannoma surgery through translabyrinthine approach.

Facial nerve function was evaluated in 103 patients, after vestibular schwannoma removal through the translabyrinthine approach. The mean follow-up was 43 months (minimum six months). Grade I facial function was achieved in 100 per cent of stage I schwannomata compared with 36 per cent of stage IV schwannomata. Grade I or II facial function was found in 78 per cent of homogeneous schwannomata, compared with 48 per cent of heterogeneous schwannomata. Facial function was preserved in 89 per cent of cases, if the angle between the internal auditory canal and the schwannoma was > 66 degrees, compared with 54 per cent if the angle was < 66 degrees. There was 82 per cent of normal facial function when the nerve appeared normal after tumour removal, compared with 18 per cent when the nerve was traumatized. When the ratio (stimulation threshold at the internal auditory canal/stimulation threshold at brainstem) was < 2, post-operative facial function was preserved in 87 per cent of cases, compared with 13 per cent when the ratio was > 2.

Sinusitis in the intensive care unit patient.

A retrospective study was undertaken to determine the incidence of sinusitis as a source of fever in the intensive care unit (ICU) patient, evaluate the effectiveness of radiologic studies in diagnosing sinusitis, and develop guidelines that may help predict the result of antral lavage. Sixteen of 52 (30.7%) lavages in patients studied with plain films and 27 of 67 (40.3%) lavages in patients studied with computed tomography of the sinuses revealed purulence in the maxillary sinuses. Conversely, 23 of 30 (76.7%) of the cases with purulence in the middle meatus had purulence in the maxillary sinus (chi-squared = 27.1). If no purulence was seen, the results of the antral lavage were negative in 68 of 89 cases (76.4%). When physical examination was used in conjunction with computed tomography, 92.3% of lavages confirmed purulence in the maxillary sinus (chi-squared = 16.6). In conclusion, the most important factor in predicting a positive result with antral lavage is the presence of purulence in the middle meatus on physical examination in conjunction with the presence of sinus disease on computed tomography of the sinuses.

Endoscopic approach to traumatic visual loss.

OBJECTIVE: To review our experience with the use of endoscopic optic nerve decompression in traumatic blindness. METHOD: We did a retrospective analysis of patients with traumatic blindness that underwent endoscopic decompression of the optic canal to determine postoperative visual acuity and correlate it to preoperative visual loss and intraoperative findings. The setting was a Level I university trauma center. We identified 8 patients treated with both surgery and steroids over a 10-month period beginning in 1993 (Seven males, one female). RESULTS: Four of six patients with total blindness (no light perception) had improvements in visual acuity. In three patients, visual acuity returned to preinjury levels. One patients with total blindness was operated on 6 weeks after injury and had a visual acuity of 20/800 at 1-year follow-up. Two patients with hand motion preoperatively had improvement in visual acuity. In one patient, vision returned to normal (20/20), and in the other it improved to 20/200). Five patients were operated on after megadose steroid treatment for at least 48 hours failed; four of five noted dramatic improvements in visual acuity. CONCLUSION: The endoscopic approach may be used to successfully decompress the optic nerve in traumatic blindness.

Superior mediastinal dissection in the treatment of Hürthle cell carcinoma of the thyroid.

BACKGROUND: Hürthle cell carcinoma of the thyroid frequently metastasizes to regional lymph nodes. Delayed lymph node dissection may become necessary, adding little risk to patient survivability; however, metastatic disease to the superior mediastinum that cannot be promptly detected, represents a survival threat that deserves special attention. The purpose of this study is to review our experience in managing Hürthle cell carcinoma of the thyroid and make recommendations for appropriate treatment. PATIENTS AND METHODS: A retrospective review of 371 thyroid neoplasms seen between 1987 and 1994 yielded six patients with Hürthle cell carcinoma of the thyroid gland. These include three cases treated with thyroidectomy and transcervical superior mediastinal dissection (SMD) as initial treatment and three cases treated with thyroidectomy alone. RESULTS: Of the three patients treated with SMD as part of their initial treatment, one had occult micrometastases to the superior mediastinum. All three patients remain alive and disease free at least 3 years later, whereas all three patients treated with thyroidectomy alone developed superior mediastinal metastases and died of their disease. CONCLUSION: We propose that at the time of initial surgery, a transcervical SMD may prevent spread to the superior mediastinum and therefore, improve survivability.

Pediatric sino-orbital desmoid fibromatosis.

Desmoid fibromatosis is a rare tumor of the head and neck. Only five cases involving the sino-orbital region have been previously reported in the literature. In this report we describe the sixth such case, involving a 2-year-old boy, and review the literature.