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Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the autoimmunology clinic and many more are on the edge to follow. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas the former target results in neutralization of the soluble factor, the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency. Knowing the exact function of the respective components enables the risk stratification for possible infectious complications in patients treated with biologics. Much of the understanding of the function of immune cells and their associated molecules, in relation to redundancy in the immune system, is derived from studies in knockout mice. However, as mice are not men in terms of their life-expectancy, their infection exposure, or the composition of their immune system, the most useful knowledge for estimating the consequence of therapeutic intervention on immune competence comes from monitoring patients. In the current chapter, we focus on patients with a primary immunodeficiency (PID) because they provide us with a unique perspective to estimate the redundancy of a certain genetic defect for overall immune competence. These patients have inborn errors of the immune system that, in general, are due to single gene defects. Depending on the immunological pathway that is defective, patients can present with different types of (opportunistic) infectious diseases, as well as other clinical manifestations. Based on selected examples, we focus in this chapter on finding parallels in the infectious risk of autoimmune patients treated with biologics and PID patients with a defect in the immunological pathway that is affected by the respective biologic. The goal is to learn from the (dis)similarities between both patient populations in terms of safety profiles of biologic treatments.Polyclonal immunoglobulin (Ig) preparations have been used for several decades for treatment of primary and secondary immunodeficiencies and for treatment of some infections and intoxications. This has demonstrated the importance of Igs, also called antibodies (Abs) for prevention and elimination of infections. Moreover, elucidation of the structure and functions of Abs has suggested that they might be useful for targeted treatment of several diseases, including cancers and autoimmune diseases. The development of technologies for production of specific monoclonal Abs (MAbs) in large amounts has led to the production of highly effective therapeutic antibodies (TAbs), a collective term for MAbs (MAbs) with demonstrated clinical efficacy in one or more diseases. The number of approved TAbs is currently around hundred, and an even larger number is under development, including several engineered and modified Ab formats. The use of TAbs has provided new treatment options for many severe diseases, but prediction of clinical effect is difficult, and many patients eventually lose effect, possibly due to development of Abs to the TAbs or to other reasons. The therapeutic efficacy of TAbs can be ascribed to one or more effects, including binding and neutralization of targets, direct cytotoxicity, Ab-dependent complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity or others. The therapeutic options for TAbs have been expanded by development of several new formats of TAbs, including bispecific Abs, single domain Abs, TAb-drug conjugates, and the use of TAbs for targeted activation of immune cells. Most promisingly, current research and development can be expected to increase the number of clinical conditions, which may benefit from TAbs.

Although matching lumbar lordosis (LL) with pelvic incidence (PI) is an important surgical goal for adult spinal deformity (ASD), there is concern that overcorrection may lead to proximal junctional kyphosis (PJK). We introduce the upper instrumented vertebra-femoral angle (UIVFA) as a measure of appropriate postoperative position in the setting of lower thoracic to pelvis surgical correction for patients with sagittal imbalance. We hypothesize that a more posterior UIV position in relation to the center of the femoral head is associated with an increased risk of PJK given compensatory hyperkyphosis above the UIV.

In this retrospective cohort study, adult patients undergoing lower thoracic (T9-T12) to pelvis correction of ASD with a minimum of 2-year follow-up were included. UIVFA was measured as the angle subtended by a line from the UIV centroid to the femoral head center to the vertical axis. Patients who developed PJK and those who did not were compared with preoperative and postoperative UIVFA as welhe UIV is from the femoral head center after lower thoracic to pelvis surgical correction for ASD, the more patients are at risk for PJK. The greater the magnitude of posterior translation of the UIV from the femoral head center from preop to postop, the greater the likelihood for PJF.

The more posterior the UIV is from the femoral head center after lower thoracic to pelvis surgical correction for ASD, the more patients are at risk for PJK. The greater the magnitude of posterior translation of the UIV from the femoral head center from preop to postop, the greater the likelihood for PJF.Simone Peterzano mostly known as the master of Caravaggio executed frescoes in the presbytery of Garegnano Charterhouse. One fresco details a shepherd with a goiter.

Thyroid eye disease (TED) is an autoimmune condition producing ocular pain, dysmotility, and ocular structure and function changes. As disease activity changes, redness, swelling, and pain can improve, but eye comfort, appearance, and motility alterations often persist. There are limited data on chronic TED patient-reported outcomes. This study examined chronic US TED patient-reported symptoms and quality of life (QOL).

Existing data from an online survey regarding chronic TED signs/symptoms and patient QOL were retrospectively examined. The Graves' Ophthalmopathy QOL instrument (GO-QOL; 0-100, 100 = highest QOL) evaluated overall, appearance, and vision-related QOL. Influencing factors were examined by stratifying patients into low (overall QOL ≤ 50), moderate (> 50 and < 75), and high (≥ 75) QOL categories.

One hundred patients (47 women, 81 Caucasian, 45.2 ± 7.6years) were included. The duration of inactive TED was 3.0 ± 4.6years and total duration of TED was 5.8 ± 5.9years. Patients reported aocial impact long after acute TED had subsided.

TED severely impacts patient QOL, despite becoming stable and chronic. Patients reported vision and appearance impairment and psychosocial impact long after acute TED had subsided.

The aim of this study was to analyze the association and susceptibility of Single Nucleotide Polymorphisms (SNPs) in the DRD2 and BDNF genes with BED in patients with weight regain in the postoperative period of bariatric surgery.

One hundred and seventy-seven individuals who underwent bariatric surgery with weight regain were evaluated and divided into two groups according to the BED diagnostic. The individuals were submitted to an anthropometric evaluation, analysis of the presence of BED using a validated questionnaire, and blood collection for genotyping of the polymorphisms rs6265 (BDNF) and rs1800497 (DRD2) by real-time polymerase chain reaction (RT-PCR).

The presence of wild-type alleles for rs1800497 (CC) and rs6265 (GG) was more frequent in patients without BED. Nevertheless, the presence of one or two variant alleles for rs1800497 (CT + TT) and rs6265 (GA + AA) was more frequent in patients with BED. The combination of the two studied SNPs prevailed in patients with BED.

The presence of allele frequency of rs1800497 SNP in the DRD2 gene and rs6265 SNP in the BDNF gene, isolated and/or combined, indicated an additional risk for the development of BED in patients with obesity, especially in the context of weight regain.

III (evidence obtained from the case-control analytic study).

III (evidence obtained from the case-control analytic study).

We conducted post hoc analyses of biomarker results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar® Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids.

Adults with active SLE and moderate to severe rash and/or arthritis were enrolled in the primary study. Patients had active SLE despite treatment with stable glucocorticoids, antimalarials, and nonsteroidal anti-inflammatory drugs and/or immunosuppressants. Patients were randomly assigned to 80 U of RCI or placebo subcutaneously every other day for 4weeks and then twice weekly through week 24. Blood samples were analyzed for serum cytokines and complement proteins using enzyme-linked immunosorbent or Luminex assays and for circulating leukocytes using flow cytometry. Biomarker levels were reported as percentages of the baseline and were further evaluated in subgroups stratified by baseline SLE Disease Activity Index-2000 (SLEDAI-2K) scores (< 10 vs. ≥ 10), baseline anti-double-stranded DNA levels (< 15IU/mL vs. ≥ 15IU/mL), and BILAG-based Combined Lupus Assessment (BICLA) responses at week 20 and 24.

RCI treatment resulted in reduced levels of B cell-activating factor and interleukin-6 cytokines in all subgroups compared with placebo. RCI treatment also resulted in lower levels of CD19

B cells and CD19

IgD

CD27

CD95

atypical activated memory B cells than did placebo in the higher baseline disease activity subgroups and in BICLA non-responders. Furthermore, RCI treatment led to greater increases in complement component (C)3 and C4 levels than did placebo in the higher baseline disease activity subgroups and in BICLA responders.

RCI may reduce inflammation through B cell immunomodulation in patients with persistently active SLE, particularly in those with higher disease activity.

ClinicalTrials.gov identifier NCT02953821.

ClinicalTrials.gov identifier NCT02953821.

Pulmonary arterial venous malformation (PAVM) is an abnormal vascular malformation between pulmonary arteries and veins characterized by varying degrees of right-to-left shunts (RLS). Cryptogenic stroke (CS) due to paradoxical embolism (PE) caused by PAVM is relatively rare in the clinic.

We report the case of a 54-year-old right-handed woman who presented with sudden-onset left-sided limb weakness for 2h. PGE2 molecular weight A physical examination revealed normal vital signs but weakness in her left upper and lower limbs, graded as 1/5 using the Medical Research Council scale. Her National Institutes of Health Stroke Scale (NIHSS) score was 8, and her modified Rankin scale (mRS) was 4. Brain diffusion-weighted imaging showed acute infarction in the right basal ganglia and the radiation crown but brain magnetic resonance angiography found no obvious abnormality. A transcranial Doppler ultrasound with bubble study (TCD-b) found the rain curtain sign of microbubbles in the left middle cerebral artery, reflecting significant RLS.