Outcomes of Mohs micrographic surgery for periocular squamous cell carcinoma.

INTRODUCTION: Periocular cutaneous squamous cell carcinoma (cSCC) accounts for 5-10% of all eyelid malignancies. Periocular cSCC carries a low mortality rate but can be destructive to local tissues. Due to the unique function and anatomy of the eyelids, Mohs micrographic surgery (MMS) is gold standard for treating cSCC to preserve healthy tissue and reduce rates of local recurrence. In this study, we describe the success and outcomes of MMS and subsequent oculoplastic reconstruction for periocular cSCC in the North East of England. METHODS: Retrospective analysis of 34 patients who underwent MMS for periocular cSCC in the North of England between 2013 and 2020. Primary outcome measure of success is defined as no recurrence of cSCC after minimum 24 months' time elapsed post-MMS. Secondary outcome measures included analysis of disease characteristics, describing the surgical techniques utilised for oculoplastic reconstruction following MMS and surgical complications should they occur. RESULTS: Two patients (5.9%) had local recurrence of periocular cSCC. Median time elapsed since MMS was 60 months. A variety of oculoplastic surgical techniques were utilised in the repair of the Mohs defect. One patient (2.9%) developed a significant post-operative reconstruction complication. CONCLUSION: Periocular cSCC recurrence following MMS in the North of England is 5.9%, which is comparable to the literature. Significant post-operative complications following oculoplastic reconstruction of periocular MMS are very low, occurring in 2.9% of cases in this study.

Toxic epidermal necrolysis occurring with immune checkpoint inhibitors.

Nivolumab and ipilimumab are immune checkpoint inhibitors (ICIs) used in the management of advanced malignancies including malignant melanoma. Although several cutaneous adverse events have been reported with these immunotherapy agents, toxic epidermal necrolysis (TEN) secondary to ICIs is rare. We report a 67-year-old man with TEN occurring during nivolumab and ipilimumab co-therapy and review published cases to highlight the challenges in recognizing and managing these patients. ICI-induced TEN can present atypically with delayed onset in comorbid, immunosuppressed patients with an associated high mortality rate. Prompt recognition and drug withdrawal are essential to improve outcomes. High dose systemic corticosteroid has also been recommended for the management of ICI-induced TEN, unlike other drug-induced TEN for which optimal immunomodulatory treatment is still debated.

A Phase 1 dose-ranging study examining the effects of a superabsorbent polymer (CLP) on fluid, sodium and potassium excretion in healthy subjects.

BACKGROUND: CLP is an orally administered, non-absorbed, superabsorbent polymer being developed to increase fecal excretion of sodium, potassium and water in patients with heart failure and end-stage renal disease. This study was conducted to evaluate the safety of CLP, and to explore dose-related effects on fecal weight, fecal and urine sodium and potassium excretion, and serum electrolyte concentrations. METHODS: This Phase 1, open-label, dose-escalation study included 25 healthy volunteers, who were administered CLP orally immediately prior to four daily meals for 9 days at doses of 7.5, 15.0, and 25.0 g/day (n = 5/group). An additional dose group received 15.0 g/day CLP under fasting conditions, and an untreated cohort (n = 5) served as control. Twenty-four-hour fecal and urinary output was collected daily. Samples were weighed, and sodium, potassium, and other ion content in stool and urine were measured for each treatment group. Effects on serum cation concentrations, other standard laboratory values, and adverse events were also determined. RESULTS: At doses below 25.0 g/day, CLP was well tolerated, with a low frequency of self-limiting gastrointestinal adverse events. CLP increased fecal weight and fecal sodium and potassium content in a dose-related manner. Concomitant dose-related decreases in urinary sodium and potassium were observed. All serum ion concentrations remained within normal limits. CONCLUSIONS: In this study, oral CLP removed water, sodium and potassium from the body via the gastrointestinal tract in a dose related fashion. CLP could become useful for patients with fluid overload and compromised kidney function in conditions such as congestive heart failure, salt sensitive hypertension, chronic kidney disease and end stage renal disease. TRIAL REGISTRATION: NCT01944007.

Serum 25-hydroxyvitamin D levels in patients with atopic eczema and the influence of narrowband ultraviolet B phototherapy.

BACKGROUND: Narrowband ultraviolet B phototherapy (nbUVB) is an established treatment modality for patients with severe atopic dermatitis (AD) and is known to increase serum vitamin D levels (SVD). The relationship between SVD and AD remains unclear. OBJECTIVES: To assess SVD and disease severity in patients with AD before and after nbUVB and establish whether a change in SVD correlates to response to nbUVB. Methods: A single-centre, open observational study recruited 21 male and 17 female patients with AD between November and April. Eczema severity was measured using the SCORAD tool, and serum 25-hydroxyvitamin D3 levels were determined before and after nbUVB, which was administered thrice weekly. RESULTS: Nine patients had severe AD, 23 moderate and six mild, as indicated by SCORAD measurements. Seventeen patients completed the study. Median SVD increased from 45 nmol/l pre-treatment to 169 nmol/l post-treatment (95% CI 2.9­5.0 times baseline) (P < 0.0001). Mean SCORAD reduction following nbUVB was significant at 21.9 units (95% CI, 14.9­28.9) (P < 0.0001). No evidence of a relationship between change in SCORAD and change in SVD was found. LIMITATIONS: A significant number of patients failed to complete the study. CONCLUSIONS: Patients with AD are at risk of vitamin D deficiency. Correlation between this and disease severity has been postulated, but this study does not provide confirmatory evidence.

Contact allergy to sodium sulfite and its relationship to sodium metabisulfite.

BACKGROUND: Sulfites are in widespread use as preservatives/antioxidants. There is increasing recognition of allergic contact dermatitis caused by sodium metabisulfite; however, contact allergy to sodium sulfite is less well recognized. OBJECTIVES: We sought to establish the prevalence of positive patch test reactions to sodium sulfite in our patient population and investigate its relationship with sodium metabisulfite. METHODS: Over a 4-month period, 183 patients referred for patch testing were tested with sodium sulfite 1% pet. in addition to sodium metabisulfite 1% pet., which already forms part of our baseline series. RESULTS: Positive allergic reactions occurred to sodium metabisulfite in 5.5% of the tested patients and to sodium sulfite in 3.8% of the tested patients. Sixty per cent of patients with a positive reaction to sodium metabisulfite were positive to sodium sulfite. Only 1 patient (0.6%) with a negative reaction to sodium metabisulfite showed a positive reaction to sodium sulfite. CONCLUSIONS: This study shows that the majority of patients with positive reactions to sodium metabisulfite are also positive to sodium sulphite. Routinely patch testing with sodium sulfite is probably unnecessary, as most patients with positive reactions will also react to sodium metabisulfite. Clinicians should consider advising patients to avoid sodium sulfite and other sulfites when a positive allergic reaction to sodium metabisulfite occurs.

Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia.

BACKGROUND: The clinical efficacy and tolerability of linezolid were demonstrated in a previously published, randomized, double-blind, registration study comparing linezolid with vancomycin for the empiric treatment of 396 patients with nosocomial pneumonia. OBJECTIVES: The aims of this study were to obtain additional experience with linezolid and vancomycin in patients with nosocomial pneumonia and to satisfy international regulatory requirements. METHODS: Patients with pneumonia acquired after 48 hours in an inpatient facility were randomly assigned to receive either IV linezolid 600 mg or IV vancomycin 1 g every 12 hours for 7 to 21 consecutive days. Patients also received IV aztreonam 1 to 2 g every 8 hours, which could be discontinued if gram-negative pathogens were not identified. The primary efficacy variables were clinical and microbiologic outcomes in evaluable patients at the follow-up visit 15 to 21 days after the end of therapy. Results from the continuation study were analyzed separately and did not include patients from the previously reported study. RESULTS: A total of 623 patients were enrolled: 321 in the linezolid group and 302 in the vancomycin group. Mean (SD) ages were 63.1 (19.1) years and 61.9 (19.3) years, respectively. Mean (SD) Acute Physiology and Chronic Health Evaluation II scores were 14.1 (5.8) and 14.1 (6.2), respectively. There were no significant differences between the linezolid and vancomycin groups at the follow-up visit in clinical cure rates (114/168 [67.9%] and 111/171 [64.9%]) or microbiologic success rates (47/76 [61.8%] and 42/79 [53.2%]) in evaluable patients (excluding those who had indeterminate or missing outcomes). There were also no significant differences in the rates of all drug-related adverse events (14.0% and 14.0%) or those that occurred in > 1% of patients, including diarrhea (3.7% and 3.0%), nausea (0.3% and 1.3%), and rash (0.6% and 1.7%) in the linezolid and vancomycin groups, respectively. CONCLUSION: In the population studied, linezolid appeared to be as well tolerated and as effective as vancomycin, each in combination with aztreonam.

Worldwide assessment of linezolid's clinical safety and tolerability: comparator-controlled phase III studies.

Linezolid, an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens including multidrug-resistant staphylococci, enterococci, and pneumococci. Safety assessments were conducted for 2,046 linezolid-treated patients and 2,001 comparator drug-treated patients from seven controlled clinical trials comparing the activities of linezolid and comparator drugs against nosocomial and community-acquired pneumonia, skin and skin structure infections, and methicillin-resistant staphylococcal infections. Drug-related adverse events were primarily transient. The most frequent (> or = 2%) adverse events caused by linezolid and the comparator drugs were diarrhea (4.3 and 3.2%, respectively; P = 0.074), nausea (3.4 and 2.3%, respectively; P = 0.036), and headache (2.2 and 1.3%, respectively; P = 0.047). Treatment discontinuations due to drug-related events (2.4 and 1.9%, respectively), serious adverse events (11.4 and 10.6%, respectively), and deaths (4.8 and 4.9%, respectively) were similar. No clinically significant drug-related hematologic events were reported, and laboratory safety data were comparable. In the first 6 months of postmarketing surveillance, hematologic abnormalities were reported in 0.1% of linezolid-treated patients, but no irreversible blood dyscrasias were documented. The risk for transient, reversible hematologic effects from treatment with linezolid should be considered together with the clinical benefits associated with its use.

Linezolid versus ceftriaxone/cefpodoxime in patients hospitalized for the treatment of Streptococcus pneumoniae pneumonia.

Intravenous (i.v.) to oral linezolid (600 mg twice daily for both, with optional aztreonam) and a cephalosporin regimen (i.v. ceftriaxone 1 g twice daily followed by oral cefpodoxime 200 mg twice daily) were compared for the treatment of community-acquired pneumonia (CAP), with emphasis on patients with Streptococcus pneumoniae. This multicenter, randomized, open-label trial was conducted in 27 countries in 6 continents. Efficacy was assessed 12-28 d following treatment. Clinical and laboratory safety assessments were evaluated; isolates for microbiologic assessments were identified primarily by sputum or blood culture. In all treated patients (linezolid, n = 381; ceftriaxone/cefpodoxime, n = 366), linezolid had a higher clinical cure rate than ceftriaxone/cefpodoxime (83.0% vs. 76.4%, respectively; p = 0.040). S. pneumoniae was isolated in 73.2% (186/254) of patients at baseline, with similar eradication rates in the linezolid and ceftriaxone/cefpodoxime groups (88.7% vs. 89.9%, respectively; p = 0.830). Linezolid had a superior clinical cure rate (93.1% vs. 68.2%; p = 0.021) in patients with S. pneumoniae bacteremia. Logistic regression analyses revealed that linezolid-treated patients with bacteremia, pleural effusion, cardiac comorbidities, diabetes or abnormal white blood cell counts had significantly better outcomes than cephalosporin-treated patients. Both regimens were well tolerated, although the incidence of drug-related adverse events was higher in the linezolid group than in the ceftriaxone/cefpodoxime group (21.3% vs. 11.2%, respectively; p = 0.0002). In summary, empiric i.v./oral linezolid was more effective than ceftriaxone/cefpodoxime in patients hospitalized with CAP, with comparable cure rates in S. pneumoniae pneumonia and higher cure rates in pneumonia complicated by bacteremia.

Dose--Response Study of Colestipol Tablets in Patients with Moderate Hypercholesterolemia.

The purpose of the study was to evaluate the efficacy and safety of a new formulation of colestipol provided in table form. This was a randomized, double-blind, placebo-controlled, multicenter, dose-ranging study. A total of 196 patients with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet (NCEP Step I diet), and having mean low-density lipoprotein cholesterol (LDL-C) levels greater-than-or-equal4.14 mmol L(minus sign1) (160 mg dl(minus sign1)) and less-than-or-equal6.46 mmol L(minus sign1) (250 mg dl(minus sign1)) were studied. Study medication was taken twice daily, with breakfast and supper, for 8 weeks. The five parallel treatment groups consisted of colestipol tablets 1, 2, 4, and 8 g BID, and matching placebo tablets BID. The main outcome measures were absolute change and percent change from baseline in selected lipid, lipoprotein, and apolipoprotein measurements; LDL-C was considered primary. Statistically significant (p less-than-or-equal 0.05) dose-dependent reductions in LDL-C from 5.2% to 25.8% and in total cholesterol from 2.8% to 16.8% were observed. Colestipol tablet treatment also resulted in statistically significant dose-dependent increases in LpAl levels reaching 25.8% at 16 g day(minus sign1). The treatment was well tolerated, and no serious adverse events were reported. Colestipol administered in tablet form was efficacious in lowering LDL-C and total cholesterol and was well tolerated in patients with primary hypercholesterolemia.