High Prevalence of Obesity and Female Gender Among Patients With Concomitant Tibialis Posterior Tendonitis and Plantar Fasciitis.

UNLABELLED: The link between increased body weight and hindfoot complaints is largely based on correlation to single foot pathology. We retrospectively reviewed 6879 patients with tibialis posterior tendonitis (TPT), plantar fasciitis (PF), or both. Among patients with either TPT or PF, 1 in 11 (9%) had both. We then compared age, gender, and body mass index among these groups. Patients with both diagnoses were neither statistically older nor more obese than patients with single diagnoses. However, they were statistically more female. Given the overall high prevalence of obesity in the study population, we feel these data support the link between obesity and multiple foot pathology. LEVELS OF EVIDENCE: Prognostic, Level IV: Case series

A Comprehensive Review of Leber Hereditary Optic Neuropathy and Its Association with Multiple Sclerosis-Like Phenotypes Known as Harding’s Disease

Jehad Alorainy,1 Yara Alorfi,2 Rustum Karanjia,3– 5 Nooran Badeeb6 1College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia; 3Doheny Eye Centers, Department of Ophthalmology, David Geffen School of Medicine at UCLA, UCLA Stein Eye Institute, Los Angeles, CA, 90095-7000, USA; 4Ottawa Hospital Research Institute, the Ottawa Hospital, Ottawa, Canada; 5Doheny Eye Institute, Los Angeles, CA, USA; 6Department of Ophthalmology, University of Jeddah, Jeddah, Saudi ArabiaCorrespondence: Nooran Badeeb, Department of Ophthalmology, University of Jeddah, Jeddah, Saudi Arabia, Email [email protected]: Leber Hereditary Optic Neuropathy (LHON) stands as a distinctive maternally inherited mitochondrial disorder marked by painless, subacute central vision loss, primarily affecting young males. This review covers the possible relationship between LHON and multiple sclerosis (MS), covering genetic mutations, clinical presentations, imaging findings, and treatment options. LHON is associated with mutations in mitochondrial DNA (mtDNA), notably m.11778G>A, m.3460G>A, and m.14484T>C, affecting complex I subunits. Beyond ocular manifestations, LHON can go beyond the eye into a multi-systemic disorder, showcasing extraocular abnormalities. Clinical presentations, varying in gender prevalence and outcomes, underscore the nature of mitochondrial optic neuropathies. Hypotheses exploring the connection between LHON and MS encompass mitochondrial DNA mutations triggering neurological diseases, immunologically mediated responses inducing demyelination, and the possibility of coincidental diseases. The research on mtDNA mutations among MS patients sheds light on potential associations with specific clinical subgroups, offering a unique perspective into the broader landscape of MS. Imaging findings, ranging from white matter alterations to cerebrospinal fluid biomarkers, further emphasize shared pathological processes between LHON-MS and classical MS. This comprehensive review contributes to the understanding of the complex relationship between LHON and MS.Keywords: visual impairment, mitochondrial DNA, demyelination diseases, neuro-ophthalmolog

A Case Study of Pseudo-Neuropathic Pseudogout

Background This interesting case highlights the clinical progression of a rare disease process and the important role of a multi-disciplinary team in achieving a diagnosis and successful management plan. Case Presentation A 76-year-old male with a history of coronary artery disease, hypertension and hyperlipidemia presented as an outpatient with left foot pain and swelling. He had spent a week bicycling in Colorado one month prior to presentation. The pain was initially localized to the plantar surface of his foot and progressed to involve the lateral and dorsal aspects of the foot, as well as his great toe. The pain was accompanied by swelling of the midfoot without erythema and he was unable to bear weight. His podiatrist prescribed Ibuprofen and a foot brace for empiric treatment of tendonitis. An outpatient MRI demonstrated extensive bony edema and synovial enhancement within the midfoot, as well as severe superficial edema and peroneal tendonitis with mild subluxation. The patient was sent to the emergency department to be evaluated for osteomyelitis

Reconstruction of the esophagojejunostomy by double stapling method using EEA™ OrVil™ in laparoscopic total gastrectomy and proximal gastrectomy

Here we report the method of anastomosis based on double stapling technique (hereinafter, DST) using a trans-oral anvil delivery system (EEATM OrVilTM) for reconstructing the esophagus and lifted jejunum following laparoscopic total gastrectomy or proximal gastric resection

Jejunal perforation in gallstone ileus – a case series

<p>Abstract</p> <p>Introduction</p> <p>Gallstone ileus is an uncommon complication of cholelithiasis but an established cause of mechanical bowel obstruction in the elderly. Perforation of the small intestine proximal to the obstructing gallstone is rare, and only a handful of cases have been reported. We present two cases of perforation of the jejunum in gallstone ileus, and remarkably in one case, the gallstone ileus caused perforation of a jejunal diverticulum and is to the best of our knowledge the first such case to be described.</p> <p>Case presentations</p> <p><b>Case 1</b></p> <p>A 69 year old man presented with two days of vomiting and central abdominal pain. He underwent laparotomy for small bowel obstruction and was found to have a gallstone obstructing the mid-ileum. There was a 2 mm perforation in the anti-mesenteric border of the dilated proximal jejunum. The gallstone was removed and the perforated segment of jejunum was resected.</p> <p><b>Case 2</b></p> <p>A 68 year old man presented with a four day history of vomiting and central abdominal pain. Chest and abdominal radiography were unremarkable however a subsequent CT scan of the abdomen showed aerobilia. At laparotomy his distal ileum was found to be obstructed by an impacted gallstone and there was a perforated diverticulum on the mesenteric surface of the mid-jejunum. An enterolithotomy and resection of the perforated small bowel was performed.</p> <p>Conclusion</p> <p>Gallstone ileus remains a diagnostic challenge despite advances in imaging techniques, and pre-operative diagnosis is often delayed. Partly due to the elderly population it affects, gallstone ileus continues to have both high morbidity and mortality rates. On reviewing the literature, the most appropriate surgical intervention remains unclear.</p> <p>Jejunal perforation in gallstone ileus is extremely rare. The cases described illustrate two quite different causes of perforation complicating gallstone ileus. In the first case, perforation was probably due to pressure necrosis caused by the gallstone. The second case was complicated by the presence of a perforated jejunal diverticulum, which was likely to have been secondary to the increased intra-luminal pressure proximal to the obstructing gallstone.</p> <p>These cases should raise awareness of the complications associated with both gallstone ileus, and small bowel diverticula.</p

Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies. Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2-ND4 vs. 11 pooled NH studies used as an external control. Subjects: The LHON subjects carried the m.11778G&gt;A ND4 mutation and were aged ≥15 years at onset of vision loss. Methods: A total of 76 subjects received a single intravitreal rAAV2/2-ND4 injection in one eye and sham injection in the fellow eye within 1 year after vision loss in REVERSE and RESCUE. Both eyes were considered as treated due to the rAAV2/2-ND4 treatment efficacy observed in the contralateral eyes. Best corrected visual acuity (BCVA) from REVERSE, RESCUE, and CLIN06 up to 4.3 years after vision loss was compared to the visual acuity of 208 NH subjects matched for age and ND4 genotype. The NH subjects were from a LHON registry (REALITY) and from 10 NH studies. A locally estimated scatterplot smoothing (LOESS), non-parametric, local regression model was used to modelize visual acuity curves over time, and linear mixed model was used for statistical inferences. Main Outcome Measures: The main outcome measure was evolution of visual acuity from 12 months after vision loss, when REVERSE and RESCUE patients had been treated with rAAV2/2-ND4. Results: The LOESS curves showed that the BCVA of the treated patients progressively improved from month 12 to 52 after vision loss. At month 48, there was a statistically and clinically relevant difference in visual acuity of −0.33 logarithm of the minimal angle of resolution (LogMAR) (16.5 ETDRS letters equivalent) in favor of treated eyes vs. NH eyes (p &lt; 0.01). Most treated eyes (88.7%) were on-chart at month 48 as compared to 48.1% of the NH eyes (p &lt; 0.01). The treatment effect at last observation remained statistically and clinically significant when adjusted for age and duration of follow-up (−0.32 LogMAR, p &lt; 0.0001). Conclusions: The m.11778G&gt;A LHON patients treated with rAAV2/2-ND4 exhibited an improvement of visual acuity over more than 4 years after vision loss to a degree not demonstrated in NH studies. Clinical Trial Registration: NCT02652767, NCT02652780, NCT03406104, and NCT03295071

Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G&gt;A ND4 Mutation: Systematic Review and Indirect Comparison

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies. Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2-ND4 vs. 11 pooled NH studies used as an external control. Subjects: The LHON subjects carried the m.11778G>A ND4 mutation and were aged ≥15 years at onset of vision loss. Methods: A total of 76 subjects received a single intravitreal rAAV2/2-ND4 injection in one eye and sham injection in the fellow eye within 1 year after vision loss in REVERSE and RESCUE. Both eyes were considered as treated due to the rAAV2/2-ND4 treatment efficacy observed in the contralateral eyes. Best corrected visual acuity (BCVA) from REVERSE, RESCUE, and CLIN06 up to 4.3 years after vision loss was compared to the visual acuity of 208 NH subjects matched for age and ND4 genotype. The NH subjects were from a LHON registry (REALITY) and from 10 NH studies. A locally estimated scatterplot smoothing (LOESS), non-parametric, local regression model was used to modelize visual acuity curves over time, and linear mixed model was used for statistical inferences. Main Outcome Measures: The main outcome measure was evolution of visual acuity from 12 months after vision loss, when REVERSE and RESCUE patients had been treated with rAAV2/2-ND4. Results: The LOESS curves showed that the BCVA of the treated patients progressively improved from month 12 to 52 after vision loss. At month 48, there was a statistically and clinically relevant difference in visual acuity of −0.33 logarithm of the minimal angle of resolution (LogMAR) (16.5 ETDRS letters equivalent) in favor of treated eyes vs. NH eyes (p A LHON patients treated with rAAV2/2-ND4 exhibited an improvement of visual acuity over more than 4 years after vision loss to a degree not demonstrated in NH studies. Clinical Trial Registration: NCT02652767, NCT02652780, NCT03406104, and NCT03295071

A rare case of a retroperitoneal enterogenous cyst with in-situ adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Retroperitoneal enterogenous cysts are uncommon and adenocarcinoma within such cysts is a rare complication.</p> <p>Case presentation</p> <p>We present the third described case of a retroperitoneal enterogenous cyst with adenocarcinomatous changes and only the second reported case whereby the cyst was not arising from any anatomical structure.</p> <p>Conclusion</p> <p>This case demonstrates the difficulties in making a diagnosis as well as the importance of a multi-disciplinary approach, and raises further questions regarding post-operative treatment with chemotherapy.</p

Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G&gt;A MT-ND4 Mutation.

INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G&gt;A ND4 mutation (MT-ND4). A previous pooled analysis of phase&nbsp;3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase&nbsp;3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174. METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase&nbsp;3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies. RESULTS: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P &lt; 0.01) with a maximal follow-up of 3.9&nbsp;years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48&nbsp;months after vision loss (89.6% versus 48.1%; P &lt; 0.01) and at last observation (76.1% versus 44.4%; P &lt; 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was -&nbsp;0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P &lt; 0.0001). Treatment effect was consistent across all phase&nbsp;3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection. CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection. TRIAL REGISTRATION NUMBERS: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY)