Cytological diagnosis of nonulcerative penile neoplasms: report of two cases

Nonulcerative penile mass lesions are rare. Pathological diagnosis of these lesions would traditionally be a biopsy. We report two such primary penile lesions which were diagnosed by fine-needle aspiration cytology (FNAC). Both lesions were present in the shaft and were diagnosed as squamous cell carcinoma (SCC). The first patient had a recurrence on the penile stump of partial amputation without any ulceration. The second had a primary urethral carcinoma on the terminal penile shaft infiltrating the corpora cavernosa dorsally. Open biopsies were avoided in both cases. FNAC was associated with very little and tolerable discomfort. There were no complications. The aspirate yield was sufficient for cytological diagnosis. FNAC of nonulcerated penile lesions is safe, well tolerated, and capable of providing a cytological diagnosis. Hence, it is a very useful outpatient procedure and could be the procedure of choice for diagnosis.     

Bilateral sternalis with unusual left-sided presentation: a clinical perspective

An unusual variation creates interest among anatomists, but is a cause of concern among clinicians when it mimics a pathology. The sternalis muscle is one such variant of the anterior chest wall located subcutaneously over the pectoralis major, ranging from a few short fibers to a well-formed muscle. We observed a bilateral case, which was accompanied by an atypical presentation on the left side where a huge, bulky sternalis muscle was associated with the absence of the sternal fibers of the pectoralis major. The fibers arose as a lateral strip from the upper two-thirds of the body of the sternum and costal cartilages 2 through 6 with the intervening fascia and aponeurosis of the external oblique. The right sternalis was strap-like and was placed vertically over the sternal fibers of the pectoralis major, arising from the underlying fascia and aponeurosis of the external oblique. The sternalis muscles, on each side, converged into an aponeurosis over the manubrium that was continuous with the sternal heads of the right and left sternocleidomastoid muscle, respectively. This rare anomaly has puzzled radiologists and surgeons in confirming diagnosis, missing it all together or mistaking it for a tumor on mammography or CT scan. These findings prompted us to review its topography, development, and application in relation to the anterior chest wall.     

Delivery of macromolecules across oral mucosa from polymeric hydrogels is enhanced by electrophoresis (iontophoresis)

Objective

To develop polymeric hydrogel delivery systems for iontophorseis transfer of large molecules across buccal (porcine) mucosa.

Methods

Three hydrogels (PVA, HPMC and PVA/HPMC) were prepared as stable gels (7 mm diameter/1.5 mm thick). Quantitative (8 and 36 h) assessment of porcine buccal mucosa and the three hydrogel delivery systems, using a diffusion cell in vitro model, was carried out by UV/vis spectroscopy with three model agents (3 and 10 kDa dextrans and 12 kDa parvalbumin). Passive and iontophoresis parameters were obtained. Experimental and theoretical data were compared.

Results

Iontophoresis (30 min, 1–8 h) significantly enhanced the delivery of all model agents across four single systems (hydrogels and buccal mucosa) and three sandwich systems (hydrogels on top of buccal mucosa), as confirmed by time lag factor/enhancement ratio (TLF/ER) data. The diffusion coefficients of model agents across buccal mucosa (×10⁻¹³ m² s⁻¹) were ∼100 times lower than across single hydrogels (2.97–4.80 × 10⁻¹¹ m² s⁻¹). Solubility values of all agents across hydrogels were similar, but lower across buccal mucosa. Permeability of parvalbumin was highest across PVA, and for both dextrans across PVA/HPMC. In sandwich systems TLFs were similar for all hydrogels, but significantly lower, and ERs significantly higher, than tissue alone. Experimental and theoretical TLF data were in reasonable agreement.

Significance

The in vitro data show that iontophoresis enhanced the delivery of large molecules across polymeric hydrogel systems and buccal mucosa. This creates the opportunity of new approaches to drug delivery and opens pathways to further research for delivering therapeutic agents topically and systemically.     

Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection

BackgroundThe clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes.ObjectiveTo determine 30-day post-hospitalization outcomes following COVID-19 infection.DesignRetrospective cohort studySettingQuaternary referral hospital and community hospital in New York City.ParticipantsCOVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020.MeasurementOutcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge.ResultsThirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00–1.02]), diabetes (1.54 [1.06–2.23]), and the need for inpatient dialysis (3.78 [2.23–6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05–1.11]) and Asian race (2.89 [1.27–6.61]) were significantly associated with mortality.ConclusionsAmong patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06924-0.KEY WORDS: COVID-19, mortality, re-admission, discharge     

Designing the epitope flanking regions for optimal generation of CTL epitopes

The flanking amino acids that surround epitopes are critical for effective antigen processing and maintenance of epitope integrity. In the present study, the frequency and characteristics of each amino acid that flanked the peptides generated from the proteasomal degradation of three different subtypes of HIV-1 Gag-p24 were determined. Synthetic flanking regions were designed based on the highest and the lowest frequencies of amino acid with the ideal characteristics at positions upstream and downstream of the proteasomal cleavage site. Peptides were synthesized that contained known CD8+ CTL-epitopes from HIV-1 Gag, CMV pp65, and vaccinia proteins HRP-2, and C16, flanked by amino acid sequences specifically designed to either generate or inhibit the known CD8+ CTL-epitopes. As predicted, the known CD8+ CTL-epitopes were effectively generated from the peptides with synthetic flanking regions specifically designed to promote epitope generation in a proteasome-dependent manner. The majority of the proteasome-generated epitopes were cleaved immediately after the C-terminal amino acid of the specific CTL-epitope. The synthetic peptide sequences containing known CD8+ CTL-epitopes with the flanking regions that promote epitope generation were effectively processed and presented to epitope specific CD8+ T-cells resulting in the production of IFN-γ. These results highlight the importance of flanking regions in promoting efficient antigen processing and presentation. This concept can have important implications in vaccine design and development strategies.