The Unique Experience of a New Multidisciplinary Program for 22q Deletion and Duplication Syndromes in a Community Hospital in Florida: A Reaffirmation That Multidisciplinary Care Is Essential for Best Outcomes in These Patients.

In 2018, the first 22q11.2 multidisciplinary program in the state of Florida was created at Joe DiMaggio Children's Hospital following the new paradigm for best care of 22q11.2 deletion patients. Since inauguration, the clinic flourished despite challenges. Our 22q clinic has 149 patients ranging from ages 0-21. From that total, 138 are 22q11.2DS: 74 females and 64 males (44% Hispanics, 35% Caucasians, 11% African American, 3% Asian and 7% multiracial). Eleven patients are in the 22q11.2 duplication group; 7 females and 4 males (50% Hispanics, 30% Caucasians 10% Asian and 10% multiracial). Our multidisciplinary team has grown to include twelve different specialties to better serve our growing patient population and has adapted to the pandemic by offering virtual clinics. Although there are many 22q multidisciplinary clinics worldwide, our clinic has special characteristics. We have an ethnically diverse group of patients and a large team of mostly bilingual providers who are passionate about and have expertise on 22q Deletion/Duplication Syndromes. Our 22q clinic is based at a community hospital and counts on the partnership of local 22q patient support groups. The program is also unique in that it is now expanding to care for adult 22q patients. Our clinic is another live example of how multidisciplinary care is the best way to achieve the most optimal outcomes in 22q patients, and that if there is a passionate and dedicated team of providers willing to collaborate for these patients, a 22q multidisciplinary program can thrive, succeed and grow at a community hospital.

Robotic-Assisted Lateral Unicompartmental Knee Arthroplasty in a Patient With Nail-Patella Syndrome.

A 59-year-old woman with nail patella syndrome (NPS) presented with progressive and severe right knee pain for the past 3 years. Imaging demonstrated laterally dislocated patella, with asymmetric femoral trochlea, and advanced lateral compartment arthritis. The patient underwent robotic-assisted lateral unicompartmental knee arthroplasty (RAUKA). The patient saw marked improvements in patient-reported outcome measurements from her initial visit to the last follow-up visit. While treatment of knee osteoarthritis in patients with NPS can be difficult, especially with attempts of patellar realignment, we present a case of a patient who underwent RAUKA, with sustained improvements in patient outcomes and range of motion, at the 2-year follow-up visit. This study is the first of its kind to demonstrate the use of a novel technology in a rare condition.

Increased Medical Complications, Revisions, In-Hospital Lengths of Stay, and Cost in Patients With Hypogonadism Undergoing Primary Total Knee Arthroplasty.

BACKGROUND: Research regarding the impact of hypogonadism following primary total knee arthroplasty (TKA) is limited. Therefore, the purpose of this study is to investigate whether patients with hypogonadism undergoing primary TKA are at increased odds of (1) medical complications, (2) revisions, (3) in-hospital lengths of stay (LOSs), and (4) cost of care. METHODS: A Humana patient population consisting of 8 million lives was retrospectively analyzed from 2007 to 2017 using International Classification of Disease, 9th Revision codes. Patients were filtered by male gender and patients with hypogonadism were matched to controls in a 1:4 ratio according to age and medical comorbidities. The query yielded 8393 patients with (n = 1681) and without (6712) hypogonadism undergoing primary TKA. Primary outcomes analyzed included medical complications, revision rates, in-hospital LOS, and cost of care. Logistic regression analysis was used to calculate odds ratios (OR) of 90-day medical complications and 2-year revisions. Welch's t-test was used to test for significance in LOS and cost of care between cohorts. A P-value less than .05 was considered statistically significant. RESULTS: Hypogonadal patients undergoing primary TKA were found to have increased incidence and odds (9.45% vs 4.67%; OR 2.12, P < .0001) of developing 90-day medical complications. Hypogonadal patients undergoing primary TKA were found to have a greater incidence and odds (3.99% vs 2.80%; OR 1.89, P < .0001) of 2-year revisions. Hypogonadal patients had a 6.11% longer LOS (3.47 vs 3.27 days, P = .02) compared to controls, and incurred greater 90-day costs ($15,564.31 vs $14,856.69, P = .018) compared to controls. CONCLUSION: This analysis of over 1600 patients demonstrates that patients with hypogonadism undergoing primary TKA have greater odds of postoperative medical complications, revisions, increased LOS, and cost of care.

Loss of IDH2 Accelerates Age-related Hearing Loss in Male Mice.

Isocitrate dehydrogenase (IDH) 2 participates in the TCA cycle and catalyzes the conversion of isocitrate to α-ketoglutarate and NADP+ to NADPH. In the mitochondria, IDH2 also plays a key role in protecting mitochondrial components from oxidative stress by supplying NADPH to both glutathione reductase (GSR) and thioredoxin reductase 2 (TXNRD2). Here, we report that loss of Idh2 accelerates age-related hearing loss, the most common form of hearing impairment, in male mice. This was accompanied by increased oxidative DNA damage, increased apoptotic cell death, and profound loss of spiral ganglion neurons and hair cells in the cochlea of 24-month-old Idh2-/- mice. In young male mice, loss of Idh2 resulted in decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the inner ear. In HEI-OC1 mouse inner ear cell lines, knockdown of Idh2 resulted in a decline in cell viability and mitochondrial oxygen consumption. This was accompanied by decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the HEI-OC1 cells. Therefore, IDH2 functions as the principal source of NADPH for the mitochondrial thioredoxin antioxidant defense and plays an essential role in protecting hair cells and neurons against oxidative stress in the cochlea of male mice.

G6pd Deficiency Does Not Affect the Cytosolic Glutathione or Thioredoxin Antioxidant Defense in Mouse Cochlea.

Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP+ to NADPH and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. We investigated the roles of G6PD in the cytosolic antioxidant defense in the cochlea of G6pd hypomorphic mice that were backcrossed onto normal-hearing CBA/CaJ mice. Young G6pd-deficient mice displayed a significant decrease in cytosolic G6PD protein levels and activities in the inner ears. However, G6pd deficiency did not affect the cytosolic NADPH redox state, or glutathione or thioredoxin antioxidant defense in the inner ears. No histological abnormalities or oxidative damage was observed in the cochlea of G6pd hemizygous males or homozygous females. Furthermore, G6pd deficiency did not affect auditory brainstem response hearing thresholds, wave I amplitudes or wave I latencies in young males or females. In contrast, G6pd deficiency resulted in increased activities and protein levels of cytosolic isocitrate dehydrogenase 1, an enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate and NADP+ to NADPH, in the inner ear. In a mouse inner ear cell line, knockdown of Idh1, but not G6pd, decreased cell growth rates, cytosolic NADPH levels, and thioredoxin reductase activities. Therefore, under normal physiological conditions, G6pd deficiency does not affect the cytosolic glutathione or thioredoxin antioxidant defense in mouse cochlea. Under G6pd deficiency conditions, isocitrate dehydrogenase 1 likely functions as the principal source of NADPH for cytosolic antioxidant defense in the cochlea.SIGNIFICANCE STATEMENT Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP+ to NADPH and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. In the current study, we show that, under normal physiological conditions, G6pd deficiency does not affect the cytosolic glutathione or thioredoxin antioxidant defense in the mouse cochlea. However, under G6pd deficiency conditions, isocitrate dehydrogenase 1 likely functions as the principal source of NADPH for cytosolic antioxidant defense in the cochlea.