Changes in operative otolaryngology infections related to the COVID19 pandemic: A retrospective cohort study.

BACKGROUND: Pediatric emergency admissions fell significantly during the COVID-19 pandemic. This study investigated the changes in severe infectious complications managed by otolaryngology between the pre-pandemic period and the first year of the pandemic to determine if COVID-19 or related public health measures influenced the rate or severity of presentations managed in otolaryngology. METHODS: A retrospective chart review was conducted on pediatric patients who presented with severe infectious otolaryngology presentations (acute mastoiditis, deep neck space abscesses, and orbital complications of sinusitis) over the pre-pandemic (March 2018-February 2020) and early pandemic (March 2020-February 2021) periods. Patient characteristics, details of presentation, treatment, and outcomes were extracted from patients' charts. Independent samples t-tests/Mann-Whitney U-tests for continuous variables and Pearson chi-squared tests/Fisher's exact test for categorical variables were conducted to compare the pre vs early pandemic groups. RESULTS: There were 93 pre-pandemic and 28 early pandemic presentations. The monthly case average was significantly lower during the early pandemic period than the 2 years prior [3.58 (2.80) vs 2.00 (2.00), P = .045]. The average monthly frequency of presentations for deep neck space abscess and mastoiditis were significantly higher in the pre-pandemic group when compared to the early pandemic group [1.96 (±0.33) vs 1.33 (±0.48), P = .049; .71 (±0.26) vs 0.17 (±0.41), P = .01, respectively]. The early pandemic group was significantly younger (3.81 vs 6.04 years, P = .005), however there were no differences in gender, length of admission, and days from symptom onset to presentation between the two groups (P > .05). The early pandemic group had significantly elevated inflammatory markers on presentation [CRP, WBC, neutrophils (P = .02, P = .02, P = .04, respectively)] compared to the pre-pandemic group. CONCLUSION: The COVID-19 pandemic has had an effect on severe infectious complications of ENT pathologies, including decreased average monthly cases during the early pandemic, younger age at presentation, and elevated inflammatory markers.

Lysosomes and the pathogenesis of merosin-deficient congenital muscular dystrophy.

Congenital muscular dystrophy type 1A (MDC1A), the most common congenital muscular dystrophy in Western countries, is caused by recessive mutations in LAMA2, the gene encoding laminin alpha 2. Currently, no cure or disease modifying therapy has been successfully developed for MDC1A. Examination of patient muscle biopsies revealed altered distribution of lysosomes. We hypothesized that this redistribution was a novel and potentially druggable aspect of disease pathogenesis. We explored this hypothesis using candyfloss (caf), a zebrafish model of MDC1A. We found that lysosome distribution in caf zebrafish was also abnormal. This altered localization was significantly associated with fiber detachment and could be prevented by blocking myofiber detachment. Overexpression of transcription factor EB, a transcription factor that promotes lysosomal biogenesis, led to increased lysosome content and decreased fiber detachment. We conclude that genetic manipulation of the lysosomal compartment is able to alter the caf zebrafish disease process, suggesting that lysosome function may be a target for disease modification.

Deep learning for image analysis: Personalizing medicine closer to the point of care.

The precision-based revolution in medicine continues to demand stratification of patients into smaller and more personalized subgroups. While genomic technologies have largely led this movement, diagnostic results can take days to weeks to generate. Management at, or closer to, the point of care still heavily relies on the subjective qualitative interpretation of clinical and diagnostic imaging findings. New and emerging technological advances in artificial intelligence (AI) now appear poised to help bring objectivity and precision to these traditionally qualitative analytic tools. In particular, one specific form of AI, known as deep learning, is achieving expert-level disease classifications in many areas of diagnostic medicine dependent on visual and image-based findings. Here, we briefly review concepts of deep learning, and more specifically recent developments in convolutional neural networks (CNNs), to highlight their transformative potential in personalized medicine and, in particular, diagnostic histopathology. Understanding the opportunities and challenges of these quantitative machine-based decision support tools is critical to their widespread introduction into routine diagnostics.

Urothelial carcinoma involving the distal penis.

Urothelial carcinoma (UC) rarely metastasizes to the penis and skin. We report the case of a 73-year-old man with UC metastases to the corpus spongiosum and dermis of the distal penis. We also review the clinicopathologic characteristics and management options for UC metastasizing to the penis. The patient presented with priapism and edema of the genital region. This follows a 5-year history of urothelial carcinoma in situ that progressed to invasive cancer despite intravesical immunotherapy. Seventeen months prior to presentation, the patient underwent a radical cystectomy with adjuvant chemotherapy. The cystectomy specimen demonstrated a pT4a N2 M0 G3 UC and margins were positive for carcinoma in situ. Follow-up had been negative for recurrence until his presentation with priapism. Incisional biopsy of the glans revealed UC and radical penectomy was performed with negative margins. The penile specimen demonstrated extensive involvement of the corpus spongiosum by UC with lymphovascular invasion and subepidermal involvement. Three months after penectomy, the patient presented with inguinal nodal recurrence. Palliative radiotherapy was administered and the patient passed away eight months after surgery.

Clinical decision analysis: Incorporating the evidence with patient preferences.

Decision analysis has become an increasingly popular decision-making tool with a multitude of clinical applications. Incorporating patient and expert preferences with available literature, it allows users to apply evidence-based medicine to make informed decisions when confronted with difficult clinical scenarios. A decision tree depicts potential alternatives and outcomes involved with a given decision. Probabilities and utilities are used to quantify the various options and help determine the best course of action. Sensitivity analysis allows users to explore the uncertainty of data on expected clinical outcomes. The decision maker can thereafter establish a preferred method of treatment and explore variables which influence the final clinical outcome. The present paper reviews the technique of decision analysis with particular focus on its application to clinical decision making.

Outcome of third renal allograft retransplants versus primary transplants from paired donors.

BACKGROUND: Third kidney retransplants have technical and immunologic hurdles that may preclude success, which is of particular importance in the contemporary context of discrepancy between organ supply and demand. METHODS: The outcomes of third renal transplant recipients (TRTR) were compared with those receiving a first transplant from paired donor kidneys to assess transplant success and complication rates. The Ontario-based Trillium Gift of Life Network database was used to identify deceased donors (n=28) who donated one kidney to a TRTR and the mate kidney to a primary renal transplant recipient (PRTR) from June 1977 to August 2006. RESULTS: As anticipated, TRTR were sensitized versus PRTR based on % panel reactive antibodies (24%+/-34% vs. 7%+/-14%, P=0.03). Delayed graft function (46% vs. 22%, P=0.05) and biopsy-proven rejection episodes (50% vs. 29%, P=0.01) occurred more frequently with TRTR despite greater frequency of induction therapy (74% vs. 35%, P=0.004). However, 1- and 5-year patient survival were similar at 93%, 83% and 96%, 87% for TRTR and PRTR, respectively. Accordingly, 1- and 5-year allograft survival censored for mortality, were comparable at 78%, 66% and 78%, 75%. Renal function was similar in both groups. Bacterial infections (43% vs. 18%, P=0.001) and wound problems (28% vs. 11%, P=0.09) were the only postoperative complications to occur more frequently in the TRTR. CONCLUSION: We conclude that third renal transplantation should not be discouraged based on functional outcomes alone.