Total Parathyroidectomy Without Autotransplantation for ESRD Patients With Secondary Hyperparathyroidism; an Effective Alternative.

BACKGROUND: The most common operations performed for secondary hyperparathyroidism include subtotal parathyroidectomy (STPX) and total parathyroidectomy with autotransplantation (TPX + AT). We present a series of ESRD patients treated with total parathyroidectomy without autotransplantation (TPX). METHODS: This is a retrospective cohort analysis of ESRD patients, age 18 years or older, with three or more glands resected on final pathology and follow-up parathyroid hormone levels obtained up to 1.5 years postoperatively. The primary endpoint was recurrence of hyperparathyroidism (defined as PTH > 500 pg/mL). RESULTS: The incidence of recurrent hyperparathyroidism at 1.5 years was 5.9% (2/34). The incidence of persistent hyperparathyroidism at 1.5 years was 11.8% (4/34). In this series, no patients were hospitalized for symptomatic hypocalcemia or experienced pathologic bone fractures. CONCLUSIONS: Recurrence rates are low with TPX. The most common cause of recurrent and persistent disease is resection of three rather than four glands. The known complications of TPX, pathologic fractures, and severe hypocalcemia, were not seen in this study.

Endoscopic Over Under Cartilage Tympanoplasty Is Not Inferior to Underlay Cartilage Tympanoplasty.

Objective: Evaluate whether elevating the tympanic membrane from the malleus during endoscopic tympanoplasty may negatively affect postoperative hearing outcomes or perforation rates by comparing 2 similar endoscopic tympanoplasty techniques. Study Design: Retrospective cohort. Setting: Tertiary care center. Patients: Endoscopic over-under cartilage tympanoplasties age and gender matched to endoscopic underlay cartilage tympanoplasties between January 2015 and January 2019. Exclusion criteria included preoperative or intraoperative cholesteatoma, performance of mastoidectomy or ossicular chain reconstruction, and lack of postoperative audiogram. Interventions: Endoscopic cartilage tympanoplasty via over-under or underlay technique. Main Outcome Measures: Pre- and postoperative pure-tone average and word recognition score, graft success. Results: A total of 52 patients were evaluated: 26 endoscopic over-under cartilage tympanoplasties were matched to endoscopic underlay cartilage tympanoplasties. Both groups demonstrated a statistically significant improvement in air conduction hearing (9 dB [P < 0.001] and 6 dB [P < 0.01], respectively), and bone pure-tone average did not worsen in either group (P < 0.001 and P < 0.05, respectively). Postoperative air conduction pure-tone average was statistically noninferior in the over-under group compared with the underlay group (P < 0.05). Reperforation was present in 3 patients (12%) in the underlay group and none in the over-under group, but this difference was not statistically significant (P = 0.24). Conclusions: Endoscopic over-under cartilage tympanoplasty effectively closes tympanic membrane perforations and improves hearing, without greater risk than underlay tympanoplasty. Elevating the tympanic membrane from the malleus does not confer worsen hearing outcomes.

A comprehensive analysis of sialolith proteins and the clinical implications.

BACKGROUND: Sialolithiasis or salivary gland stones are associated with high clinical morbidity. The advances in the treatment of sialolithiasis has been limited, however, by our understanding of their composition. More specifically, there is little information regarding the formation and composition of the protein matrix, the role of mineralogical deposition, or the contributions of cell epithelium and secretions from the salivary glands. A better understanding of these stone characteristics could pave the way for future non-invasive treatment strategies. METHODS: Twenty-nine high-quality ductal stone samples were analyzed. The preparation included successive washings to avoid contamination from saliva and blood. The sialoliths were macerated in liquid nitrogen and the maceration was subjected to a sequential, four-step, protein extraction. The four fractions were pooled together, and a standardized aliquot was subjected to tandem liquid chromatography mass spectrometry (LCMS). The data output was subjected to a basic descriptive statistical analysis for parametric confirmation and a subsequent G.O.-KEGG data base functional analysis and classification for biological interpretation. RESULTS: The LC-MS output detected 6934 proteins, 824 of which were unique for individual stones. An example of our sialolith protein data is available via ProteomeXchange with the identifier PXD012422. More important, the sialoliths averaged 53% homology with bone-forming proteins that served as a standard comparison, which favorably compared with 62% homology identified among all sialolith sample proteins. The non-homologous protein fraction had a highly variable protein identity. The G.O.-KEGG functional analysis indicated that extracellular exosomes are a primary cellular component in sialolithiasis. Light and electron microscopy also confirmed the presence of exosomal-like features and the presence of intracellular microcrystals. CONCLUSION: Sialolith formation presents similarities with the hyperoxaluria that forms kidney stones, which suggests the possibility of a common origin. Further verification of a common origin could fundamentally change the way in which lithiasis is studied and treated.

Cochlear Enhancement May Precede Cochlear Obliteration After Vestibular Schwannoma Excision.

OBJECTIVE: Cochlear obliteration after vestibular schwannoma excision has been noted, with implications on cochlear implantation. Early postoperative cochlear enhancement with gadolinium on magnetic resonance imaging (MRI) has also been observed. Timing of enhancement and association with obliteration is described here. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center, ambulatory. PATIENTS: Patients receiving vestibular schwannoma excision surgery by the senior author performed at one institution between January 2015 and July 2017 with postoperative MRIs INTERVENTION:: Diagnostic. MAIN OUTCOME MEASURE(S): The imaging characteristics on postoperative MRIs examined were loss of fluid signal on postoperative T2 images and cochlear enhancement on gadolinium enhanced T1 images. In the patients receiving labyrinthine sparing procedures, presence of postoperative hearing was evaluated. RESULTS: Of the 42 patients evaluated, 24 received the translabyrinthine approach and 18 received a labyrinth sparing surgery. Twenty-nine had evidence of cochlear enhancement on T1 with gadolinium contrast, and 27 had evidence of cochlear obliteration on T2 images. The odds ratio of patients with cochlear enhancement having obliteration was 30.0:1 (p < 0.0001). Intense cochlear enhancement (n = 21) appeared a median of 163 days after surgery, and complete or near complete obliteration (n = 18) appeared a median of 480 days after surgery, a statistically significant difference (p < 0.001). Within the labyrinth sparing group, there was no statistically significant association between hearing loss and cochlear obliteration or enhancement. CONCLUSIONS: Cochlear enhancement is correlated with cochlear obliteration and may precede it.

Retro-Auricular Thyroidectomy: An Open Approach.

Distant access robot-assisted thyroidectomy has gained popularity in recent years. Adoption of distant access procedures has been limited by cost, need for specialized training and expertise. We report our preliminary clinical experience with our modification of the retro-auricular thyroidectomy approach that allows adequate exposure for thyroid lobectomy without robotic or endoscopic assistance. This is a retrospective chart review of ten patients who have undergone retro-auricular thyroidectomies in the absence of robotic or endoscopic assistance. Ten patients were identified to have undergone this procedure over an 18-month period. All patients were female with average age 36 years (range 27-52). Six were right sided and 4 were left sided procedures. The average gland size was 4.2 cm (range 3.7-6 cm). The average nodule size was 2.1 cm (range 1.1-3.5 cm). The average operative time was 91 min (range 76-114 min). All patients had benign pathology on final histopathology. There were no conversions to open cervical thyroidectomy. Two patients had vocal cord paresis that resolved spontaneously. The average postoperative follow up was 3 months (range 1-7 months). Our technique for retro-auricular thyroidectomy is a safe, reproducible, and cost effective option for remote access thyroidectomy.

DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA.TTC repeats in Friedreich's ataxia.

The DNA abnormality found in 98% of Friedreich's ataxia (FRDA) patients is the unstable hyperexpansion of a GAA.TTC triplet repeat in the first intron of the frataxin gene. Expanded GAA.TTC repeats result in decreased transcription and reduced levels of frataxin protein in affected individuals. Beta-alanine-linked pyrrole-imidazole polyamides bind GAA.TTC tracts with high affinity and disrupt the intramolecular DNA.DNA-associated region of the sticky-DNA conformation formed by long GAA.TTC repeats. Fluorescent polyamide-Bodipy conjugates localize in the nucleus of a lymphoid cell line derived from a FRDA patient. The synthetic ligands increase transcription of the frataxin gene in cell culture, resulting in increased levels of frataxin protein. DNA microarray analyses indicate that a limited number of genes are significantly affected in FRDA cells. Polyamides may increase transcription by altering the DNA conformation of genes harboring long GAA.TTC repeats or by chromatin opening.

Sticky DNA: in vivo formation in E. coli and in vitro association of long GAA*TTC tracts to generate two independent supercoiled domains.

The expanded GAA*TTC repeat sequence associated with Friedreich's ataxia (FRDA) adopts non-B DNA structures, (triplexes and sticky DNA). Sticky DNA is formed in plasmids by the association of two long GAA*TTC tracts at lengths that are found in the sequence of the frataxin gene in patients. Most FRDA patients have expanded GAA*TTC repeats (up to 1700 triplets), which inhibit the transcription of the gene, thus diminishing the synthesis of frataxin, a mitochondrial protein involved in iron-sulfur cluster biogenesis. Negative supercoiling and MgCl(2) (or MnCl(2)) are required to stabilize sticky DNA (a dumbbell-shaped structure) in plasmids with a pair of repeat tracts where n> or =60 in the direct repeat orientation in vitro. Since the triplet repeat sequences (TRS) were symmetrically positioned in the plasmids and because a number of unique restriction sites were present in the vector, studies were conducted to evaluate the influence of selectively linearizing one or the other supercoiled domains created by the DNA*DNA associated region, i.e. the stable complex at the pair of TRS's. The two domains behave independently, thus confirming the association of the two tracts and the dumbbell-shaped plasmid in our model for sticky DNA. Linking number investigations were performed on a family of plasmids harboring different lengths (30, 60, or 176 repeats), orientations and number of tracts (one or two) of a GAA*TTC repeat in Escherichia coli to evaluate the in vivo role, if any, of sticky DNA. Unexpectedly, this non-B DNA conformation elicited the formation of a TRS-length dependent change in the global topology of the plasmids, indicative of an apparent compression of the primary helices. Thus, linking number determinations confirm that sticky DNA has an important consequence in vivo.

Advances in mechanisms of genetic instability related to hereditary neurological diseases.

Substantial progress has been realized in the past several years in our understanding of the molecular mechanisms responsible for the expansions and deletions (genetic instabilities) of repeating tri-, tetra- and pentanucleotide repeating sequences associated with a number of hereditary neurological diseases. These instabilities occur by replication, recombination and repair processes, probably acting in concert, due to slippage of the DNA complementary strands relative to each other. The biophysical properties of the folded-back repeating sequence strands play a critical role in these instabilities. Non-B DNA structural elements (hairpins and slipped structures, DNA unwinding elements, tetraplexes, triplexes and sticky DNA) are described. The replication mechanisms are influenced by pausing of the replication fork, orientation of the repeat strands, location of the repeat sequences relative to replication origins and the flap endonuclease. Methyl-directed mismatch repair, nucleotide excision repair, and repair of damage caused by mutagens are discussed. Genetic recombination and double-strand break repair advances in Escherichia coli, yeast and mammalian models are reviewed. Furthermore, the newly discovered capacities of certain triplet repeat sequences to cause gross chromosomal rearrangements are discussed.