Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics.

Exudates of nonhealing wounds contain drivers of pathogenicity. We utilized >800 exudates from nonhealing and healing wounds of diverse etiologies, collected by 3 different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to (i) differentiate between healing and nonhealing wounds, (ii) follow the healing process of individual patients, and (iii) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically nonhealing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo nonhealing wound exudates revealed an induction of inflammatory cytokine and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of nonhealing wounds. Testing the wound therapeutics, PDGF and silver sulfadiazine, yielded responses in line with clinical experience and indicates the usefulness of the assay to search for and profile new therapeutics.

Oral fusidic acid for the treatment of mild-to-moderate hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease. Tetracyclines are one of the few therapeutic options recommended for mild-to-moderate disease. This study aimed to investigate the efficacy of systemic fusidic acid's (FA) effectiveness in treating HS. METHODS: This retrospective study analyzed 55 FA therapy cycles (TC, average weekly dose: 6409 mg; range: 5250-9800 mg; 2-12 weeks) in 49 patients. The outcome was evaluated using the Physician's Global Assessment (PGA) scale. Therapy response was defined as any reduction of inflammatory activity without the occurrence of flares. We also characterized adverse events and investigated predictors for treatment success. Results were compared to a matched control group receiving doxycycline. RESULTS: FA treatment (55 treatment cycles (TC); male: 45.5%; female: 54.5%) showed an overall response rate of 70.9% (39 TC). No worsening was observed. Significantly higher response rates were observed in females (83.3%, P = 0.026) and Hurley I (90.9%, P = 0.008). After multivariate adjustment, higher response rates were associated with the Hurley grade (P = 0.046) but not with gender (P = 0.0174). Adverse reactions (21.8% gastrointestinal symptoms) occurred in 27.3% (15 TC) and 46.7% within the first 4 weeks. Similar results were observed in the doxycycline control group (overall response rate: 76.4%). CONCLUSION: Oral FA is safe and improves symptoms in most patients. HS patients could benefit from oral FA treatment, especially in case of contraindications or resistance to tetracyclines.

Dispensing anti-osteoporotic drugs changed during the COVID-19 pandemic.

OBJECTIVES: Caring for osteoporosis patients has proven challenging during the COVID-19 pandemic due to repeated lockdowns in Austria. The distinct possibility of insufficient treatment regimens is therefore a matter of pressing concern. The aim of the study was to assess alterations in dispensing anti-osteoporotic drugs during the COVID-19 pandemic. PATIENTS/METHODS: This study was a nationwide retrospective register-based observational study which included all patients in Austria aged ≥50 who received at least one prescription for anti-osteoporotic medication between January 2016 and November 2020. Pseudonymised individual-level patients' data were obtained from social insurance authorities. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) to predict drug dispensing. RESULTS: There were 2,884,374 dispensations of anti-osteoporotic drugs to 224,598 patients between 2016 and 2020. The mean monthly prescriptions for oral bisphosphonates (-14.5 %) and SERMs (-12.9 %) decreased during the COVID-19 pandemic when compared to the non-COVID-19 period. Dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased. Prescriptions for DMAB decreased during the first lock-down, however increased by 29.1 % for the total observation time. The Arima models showed that in March 2020 (beginning of the 1st COVID-19 lockdown), there was a decrease of 778 dispensings, with a further increase of 14 dispensings every month for denosumab; a decrease by 178 dispensings, with a further increase of 23 dispensings every month for zolendronic acid; a decrease by 2950 dispensings, but with a further increase of 236 dispensings every other month for ibandronate and a decrease by 1443 dispensing with a further decrease of 29 dispensings for alendronate than predicted, had the lockdown not occurred. CONCLUSIONS: The total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during first COVID-19 lockdown. The observed decrease of DMAB during the first lockdown rebounded in the following months. Considering the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even during a pandemic.

Cytomegalovirus Colitis Masquerading as Apple-Core Lesion after Systemic Chemotherapy in a Patient with Relapsed Acute Myeloid Leukemia.

We report the case of a 71-year-old male with relapsed acute myeloid leukemia who developed cytomegalovirus (CMV) colitis presenting as an apple-core lesion during induction chemotherapy. CMV infection occurs rarely during induction chemotherapy for acute myeloid leukemia. CMV infection is usually observed in patients with acquired immune deficiency syndrome (AIDS) and in those on immunosuppressive agents following bone marrow transplant. Although rare, CMV colitis should be considered in patients who are critically ill after systemic chemotherapy as it can cause significant morbidity and mortality.

Phrynoderma and acquired acrodermatitis enteropathica in breastfeeding women after bariatric surgery.

BACKGROUND AND OBJECTIVES: Women who have undergone bariatric surgery are susceptible to nutritional deficiencies in subsequent pregnancies. We highlight the importance of dermatologists in the early recognition of cutaneous signs of malnutrition occurring in this specific clinical setting. PATIENTS AND METHODS: We compare clinical characteristics of two young women with dermatological signs of combined post-gestational nutritional deficiencies following Roux-en-Y gastric bypass surgery. RESULTS: Patient 1 exhibited follicular papules on the extremities, perianal eczema, perlèche, alopecia, and depigmentation of hair. Patient 2 showed erythematous plaques in genitoanal and acral areas, perlèche, diffuse alopecia, and depigmentation of hair. Based on clinical and histopathological findings, decreased vitamin A (patient 1) and zinc levels (patient 2), we diagnosed phrynoderma and acquired acrodermatitis enteropathica, respectively. Comparison of the two patients revealed that both (i) were lacking follow-up after gastric bypass surgery, (ii) developed skin lesions as primary symptoms with (iii) mixed clinical manifestations due to combined deficiencies, and (iv) experienced initial symptoms during lactation suggesting a causal relationship. CONCLUSIONS: Our observations highlight the potentially increased risk of women to develop post-gestational dermatological manifestations of malnutrition following bariatric surgery. The awareness of dermatologists with respect to this emerging, susceptible patient group may help avert damage to mother and child.

Multiregion thermal sensitivity mapping of the hand.

Previous neurophysiological studies of discrete hand regions have suggested the dorsum to be more sensitive to temperature changes than the palmar surface, but no multiple-region investigation of the corresponding dorsal and palmar regions has been performed. This study aimed to investigate whether the dorsum of the hand is more sensitive to temperature changes than the palm across multiple regions. In 15 healthy human volunteers, cold and warmth detection thresholds were measured in 10 defined areas of the hand using a thermode of 2.56 cm(2). The testing algorithm employed was the Method of Limits with a baseline temperature of 32 °C and a rate of change of 1°/s. In five subjects, cold-pain and heat-pain thresholds were also measured. All dorsal regions were significantly more sensitive to cold than equivalent palmar areas. Differences in warmth thresholds were not uniform but, overall, dorsal sensitivity was significantly higher. This study finds that the dorsal aspect of the hand was more sensitive to temperature changes than the palm, with higher sensitivity to painful thermal stimuli.

Clinical application of pectoral nerve transfers in the treatment of traumatic brachial plexus injuries.

PURPOSE: To determine the effectiveness, reliability and donor site morbidity of pectoral nerve transfers in the treatment of brachial plexus lesions. METHODS: This retrospective study included 6 patients with 7 pectoral nerve transfers. The follow-up examination comprised measurement of the ranges of motion (AO neutral-0 method), functional muscle testing (British Medical Research Council), and photo- and videographic documentation. RESULTS: Three patients achieved excellent results (M5, M4), in 3 cases good muscle function was achieved (M3) and 1 patient, who had a short follow-up period, revealed M2 motor function. CONCLUSIONS: This study describes the treatment of patients with conditions far from ideal. All patients sustained extensive brachial plexus lesions and most had severe associated injuries of the upper limb, which limited the availability of sufficient donor nerves. Despite these facts, 6 cases had excellent or good results and 1 showed continuing improvement of muscle function. These good results and the excellent results documented in literature demonstrate the high dependability and efficiency of the pectoral nerves as donors in the treatment of brachial plexus lesions. Furthermore, it was shown that free functioning muscle transplants can be sufficiently reinnervated by pectoral nerves. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.