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1.
J Pediatr Surg ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38522977

ABSTRACT

PURPOSE: Costal cartilage resection with or without rib resection is the gold standard surgery for slipping rib syndrome. Minimally invasive restoration of normal anatomy via nonabsorbable sutures has been described in the adult population with encouraging results. We sought to assess the efficacy of minimally invasive sutured fixation of the hypermobile rib in the pediatric population. METHODS: A retrospective review was performed at Mayo Clinic involving 31 pediatric patients diagnosed with slipped rib syndrome. Minimally invasive sutured open reduction internal fixation was performed between 2020 and 2022. The standardized Örebro Musculoskeletal Pain Screening Questionnaire was given at dedicated time points pre- and post-operatively to assess efficacy. Significance was determined via the Wilcoxon rank sum test. RESULTS: SRS was diagnosed clinically in 31 patients (24 females, 7 males, 1220 years-old). Symptoms were present for an average of 18.9 months and patients had seen an average of 4.7 specialists. Traumatic causes were identified in three patients and eight patients had hypermobility. At one month follow up, there were no surgical complications and patients reported significantly less pain (p < 0.001). Preoperative analgesics reduced by 80%. Ultimately, seven patients underwent a second operation; three patients underwent a third operation; one patient underwent five total operations. Recurrent pain was reported in six patients. Only nine patients followed-up at 1-year post-operation. CONCLUSION: Pediatric patients with SRS demonstrated an early positive response to suture fixation without costal cartilage excision. Reoperation and recurrent pain, however, remain significant in this population. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Case series with no comparison group.

2.
BMJ Case Rep ; 17(2)2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38367992

ABSTRACT

Intussusception following Roux-en-Y gastric bypass is a rare, potentially life-threatening complication. Patients present with intermittent obstructive symptoms, and the diagnosis is made on imaging. Treatment is surgical considering the high likelihood of non-operative failure, strangulation, incarceration, perforation and concern for malignancy. We present the case of a woman in her 60s with a history of Roux-en-Y gastric bypass who presented with retrograde jejunojejunal intussusception at the distal Roux anastomosis. She proceeded to the operating room for complete anastomotic resection with reconstruction of three blind ends via two sequential isoperistaltic anastomoses. She progressed appropriately throughout her hospitalisation and was discharged on postoperative day 5 without recurrence. While intussusception in Roux-en-Y anatomy has been previously described, a literature review yielded sparse results in detailing its surgical correction. We highlight our unique surgical approach of jejunojejunal anastomotic resection with the creation of sequential isoperistaltic side-to-side anastomoses.


Subject(s)
Gastric Bypass , Gastrointestinal Diseases , Intussusception , Female , Humans , Anastomosis, Roux-en-Y/adverse effects , Gastric Bypass/adverse effects , Gastrointestinal Diseases/etiology , Intussusception/diagnostic imaging , Intussusception/etiology , Intussusception/surgery , Middle Aged , Aged
3.
AME Case Rep ; 8: 24, 2024.
Article in English | MEDLINE | ID: mdl-38234347

ABSTRACT

Background: Chylothoraces result from traumatic or non-traumatic insult to the thoracic duct, allowing for lymph to accumulate in the chest. Patients present with increasing dyspnea and fatigue, and the diagnosis is made via chest X-ray, computed tomography (CT), and comparative analysis of the pleural fluid and serum. Management largely entails diet modification and drainage with or without adjunct medications, reserving pleurodesis, percutaneous duct embolization, or thoracic duct ligation for recalcitrant cases. Case Description: A 72-year-old female presented with a 10-year history of recurrent chylothorax. This was precipitated by a rib biopsy in 2013 for concerns of fibrous dysplasia, which was complicated by pneumothorax requiring chest tube placement and recurrent chylous effusion. The patient remained minimally symptomatic despite its chronicity. The lymphatic leak fistulized into her right breast in 2019 to cause significant swelling and exacerbate discomfort. Upon presentation, she noted incessant dyspnea, right arm and breast lymphedema, and exercise intolerance. Initial treatment involved placement of an indwelling pleural catheter (IPC) and interventional radiology (IR)-guided thoracic duct embolization. When persistent, she proceeded with video-assisted thorascopic surgery (VATS) decortication, talc pleurodesis, and ligation of the chylous leak. She was discharged with a drain that remained for one month until sinograms displayed resolution of the effusion. Conclusions: Optimal chylothorax management remains debatable as it is understudied with few high-quality trials guiding treatment. When conservative management is unsuccessful, procedural intervention is often required to minimize morbidity and mortality. A literature review yielded sparse similarities between our case and others, highlighting the irregularity of presentation, challenges faced, and importance of a multidisciplinary approach in management.

5.
Bioorg Med Chem Lett ; 29(16): 2224-2228, 2019 08 15.
Article in English | MEDLINE | ID: mdl-31248774

ABSTRACT

This letter describes progress towards an M4 PAM preclinical candidate inspired by an unexpected aldehyde oxidase (AO) metabolite of a novel, CNS penetrant thieno[2,3-c]pyridine core to an equipotent, non-CNS penetrant thieno[2,3-c]pyrdin-7(6H)-one core. Medicinal chemistry design efforts yielded two novel tricyclic cores that enhanced M4 PAM potency, regained CNS penetration, displayed favorable DMPK properties and afforded robust in vivo efficacy in reversing amphetamine-induced hyperlocomotion in rats.


Subject(s)
Aldehyde Oxidase/metabolism , Myotonia Congenita/metabolism , Receptor, Muscarinic M4/metabolism , Animals , Drug Discovery , Humans , Rats , Structure-Activity Relationship
6.
ACS Chem Neurosci ; 9(7): 1520-1529, 2018 07 18.
Article in English | MEDLINE | ID: mdl-29695153

ABSTRACT

After the identification of the influence of serotonergic receptors in ameliorating the negative symptoms associated with schizophrenia, atypical antipsychotics were developed by incorporating dopamine and serotonin antagonism. Risperidone, sold under the trade name Risperdal, was the second atypical antipsychotic developed following clozapine but quickly became a first-line treatment for acute and chronic schizophrenia because of its preferential side effect profile. Despite initial Food and Drug Administration approval 25 years ago, risperidone continues to be a fundamental treatment for schizophrenia, bipolar I disorder, and autism-related irritability. It is on the World Health Organization's List of Essential Medicines for its balance of efficacy, safety, tolerability, and cost-effectiveness. In this review, we highlight the history and importance of risperidone as an atypical antipsychotic, in addition to its chemical synthesis, manufacturing, drug metabolism and pharmacokinetics, pharmacology, structure-activity relationship, indications, and adverse effects.


Subject(s)
Risperidone/therapeutic use , Serotonin Antagonists/therapeutic use , Animals , Humans , Mental Disorders/drug therapy , Risperidone/adverse effects , Risperidone/chemistry , Risperidone/pharmacology , Serotonin Antagonists/adverse effects , Serotonin Antagonists/chemistry , Serotonin Antagonists/pharmacology
7.
Org Lett ; 19(20): 5693-5696, 2017 10 20.
Article in English | MEDLINE | ID: mdl-28976768

ABSTRACT

N-Alkyl substituted chlorotetrazines were coupled with various boronic acids under Suzuki conditions in high yield at room temperature, giving a mild and straightforward synthetic route toward diverse unsymmetrical 1,2,4,5-tetrazines, a rare heteroarene. This chemistry not only expands the known substrate scope of tetrazine cross-coupling reactions but also allows for the synthesis of novel, tetrazine-containing biologically active molecules with improved DMPK properties.

8.
Angew Chem Int Ed Engl ; 55(34): 9974-8, 2016 08 16.
Article in English | MEDLINE | ID: mdl-27384522

ABSTRACT

The Cδ -H amination of unactivated, secondary C-H bonds to form a broad range of functionalized pyrrolidines has been developed by a triiodide (I3 (-) )-mediated strategy. By in situ 1) oxidation of sodium iodide and 2) sequestration of the transiently generated iodine (I2 ) as I3 (-) , this approach precludes undesired I2 -mediated decomposition which can otherwise limit synthetic utility to only weak C(sp(3) )-H bonds. The mechanism of this triiodide-mediated cyclization of unbiased, secondary C(sp(3) )-H bonds, by either thermal or photolytic initiation, is supported by NMR and UV/Vis data, as well as intercepted intermediates.


Subject(s)
Amines/chemical synthesis , Iodides/chemistry , Pyrrolidines/chemistry , Amination , Amines/chemistry , Cyclization , Molecular Structure
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