A global call for action to tackle skin-related neglected tropical diseases (skin NTDs) through integration: An ambitious step change.

On 8 June 2022, the World Health Organization (WHO) released pivotal guidance, "Ending the neglect to attain the Sustainable Development Goals: A strategic framework for integrated control and management of skin-related neglected tropical diseases." Skin-related neglected tropical diseases, or skin NTDs, comprise a group of NTDs that produce signs and symptoms on the skin and include at least 9 diseases or disease groups. Moving away from disease-specific approaches, it is anticipated that synergies will be identified and integrated building on this shared feature, where possible, to achieve a greater health impact. This paper intends to draw attention to the prospects created by this scheme. The framework is a key basis for a proposal produced by WHO dedicated to skin NTD integration and describes the practical opportunities for this evolving strategy. It underlines the wider health benefits that will follow, thus working towards Universal Health Coverage and skin health for all.

A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: Skin lesion morphology, clinical course, and scarring.

BACKGROUND: In the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. OBJECTIVE: The objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. METHODS: The American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals. RESULTS: From August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases. LIMITATIONS: Registry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity. DISCUSSION: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.

WhatsApp platforms in tropical public health resource-poor settings.

In order to deliver equal healthcare access to resource-poor settings, sustainable, cost-effective systems of communication should be used. As mobile phone use increases, remote care can be delivered via teledermatology using Apps. This commentary covers how WhatsApp could be used by dermatologists seeking to deliver healthcare in this context.

A rapid method for determining salinomycin and monensin sensitivity in Eimeria tenella.

Standard methods of determining the ionophore sensitivity of Eimeria rely on infecting chickens with an isolate or a mixture of Eimeria spp. oocysts in the presence of different anti-coccidial drugs. The purpose of this study was to develop a rapid in vitro method for assessing salinomycin and monensin sensitivity in Eimeria tenella. Cultures of MDBK cells were grown to 85% confluency, and then inoculated with excysted E. tenella laboratory strain (APU-1) sporozoites in the presence of different concentrations of salinomycin or monensin. At various timepoints, the monolayers were fixed for counting intraceullar sporozoites, or were subjected to DNA extraction, followed by molecular analysis using quantitative (qPCR) or semi-quantitative PCR (sqPCR). Preliminary experiments showed that 24h was the optimum time for harvesting the E. tenella-infected cell cultures. The average number of E. tenella sporozoites relative to untreated controls displayed a linear decrease between 0.3 and 33.0 µg/ml salinomycin and between 0.3 and 3.3 µg/ml monensin. A similar pattern was observed in the relative amount of E. tenella DNA as measured by sqPCR. A linear decrease in the relative amount of E. tenella DNA was observed over the entire range of salinomycin and monensin concentrations as measured by qPCR possibly reflecting the greater sensitivity of this assay. Comparison of sporozoite counting, sqPCR, and qPCR signals using a criterion of 50% inhibition in sporozoite numbers or level of PCR amplification product showed good agreement between the three assays. E. tenella field isolates (FS-1 and FS-2) displaying resistance to salinomycin and monensin were evaluated in the in vitro assay using qPCR and sqPCR. Compared to E. tenella APU-1, the E. tenella FS-1 and FS-2 isolates showed higher levels of E. tenella DNA at 24h by both qPCR and sqPCR. This in vitro assay represents a significant advance in developing rapid, cost-effective methods for assessing ionophore sensitivity in E. tenella.

Assessment of skin barrier function in podoconiosis: measurement of stratum corneum hydration and transepidermal water loss.

BACKGROUND: Podoconiosis is a common cause of lymphoedema in barefoot workers in Ethiopia and other countries. It has severe consequences for patients' physical function, quality of life and economic status. AIMS: To investigate stratum corneum (SC) hydration and transepidermal water loss (TEWL) in patients with podoconiosis compared with controls. METHODS: In total, 55 patients and 20 controls were recruited. For each study subject, SC and TEWL measurements were taken, along with foot and lower leg circumferences. Measurements were compared between the patient and control groups. RESULTS: Foot circumferences tended to be higher in patients with podoconiosis, with the mean foot:leg circumference ratio being 1·19 (95% confidence interval 1·11-1·28) times that for controls (P = 0·001). There was no detectable difference between patients and controls in TEWL values (P > 0·05); however, SC hydration was significantly lower in patients vs. controls for the foot (P = 0·004) and lower leg (P = 0·046) sites. CONCLUSIONS: Patients with podoconiosis have significantly lower SC hydration in the skin of their lower legs and feet than controls, which may lead to cracking and splitting, and increased risk of lymphoedema and infection.

An assessment of the effects of cadaver donor bone marrow on kidney allograft recipient blood cell chimerism by a novel technique combining PCR and flow cytometry.

A new technique, the PCR-flow assay is described that has allowed for the serial identification and quantitation of discrete mononuclear cell subsets of donor (or recipient) bone marrow derived cells in cadaver kidney transplant recipients infused postoperatively with donor vertebral body bone marrow cells. With fixed permeabilized cells in flow cytometry the amplification power of the polymerase chain reaction (PCR), using fluorescent-labeled primers to identify single copy HLA class II DRbeta1 genes of either donor or recipient origin, is combined with multi-color fluorochrome-labeled CD epitope-specific monoclonal antibodies. The details of the methodology are described; these support the utility of the assay. Initial observations were made on the chimeric makeup of the peripheral blood as well as iliac crest bone marrow between six months and one year posttransplantation in recipients serially followed weekly and then monthly, concomitantly compared with a control group of stable kidney transplant recipients using similar therapeutic protocols, who did not receive cadaver bone marrow. Several findings are of note. In 14 recipients of two bone marrow infusions totalling a mean of 6.29+/-2.18x10(10) cells, donor CD34 positive (+) (immature) cells were fourteen times as numerous in peripheral blood six months postoperatively as in six recipients given half as many bone marrow cells in one infusion (averaging 3.02+/-0.5x10(10)). These donor CD34+ cells unexpectedly averaged 36+/-7% of the total (donor plus recipient) CD34+ subset counted. Moreover, iliac crest bone marrow aspirates contained an average of thirteen times this number of CD34+ cells than in the peripheral blood, supporting the notion of engraftment. Of additional interest, between six months and one year posttransplant although no donor cells could be detected in peripheral blood of the controls there was an identifiable presence of donor CD34+ cells in their iliac crest bone marrow, albeit 10-fold less than the marrow-infused patients. In the clinical follow-up, although there were three unrelated mortalities, there were no additional kidney losses with current serum creatinine concentrations averaging 1.3+/-0.06 mg/dl. In conclusion, the PCR-flow assay presents the possibility of identifying discrete subsets of donor or recipient cells that may have an immunoregulatory function.

The prevalence of skin disease among school children in rural Ethiopia--a preliminary assessment of dermatologic needs.

It is always assumed that the prevalence of skin diseases in developing countries is very high, and that infestations and skin infections are highly endemic in poor rural communities; however, very few epidemiologic reports verify these assumptions. As part of a continuing study of dermatologic needs in southwestern Ethiopia, and to estimate the prevalence of treatable skin disease in children, a school survey was undertaken in Shebe. In October 1992, 112 children were examined by a team of dermatologists and their conditions were recorded. Twenty-two children (19.6%) were considered healthy and 90 (80.4%) had one or more skin diseases. A total of 140 conditions were identified and considered treatable in 98% of children. Infestations were the most prevalent skin pathology, 81.2%, followed by fungal infections, 13.4%.

Long term assessment of patterns of treatment failure and survival in patients with stage I or II follicular lymphoma.

BACKGROUND: Follicular lymphoma is a clearly defined type of malignant lymphoma. The many treatment approaches reported in the literature attest to the lack of agreement on its best management. The treatment experiences of patients with Stage I or II follicular lymphoma who were at risk for at least 5 years were reviewed to assess their survival, disease free survival, and patterns of failure. METHODS: Between 1974 and 1988, 144 patients with Stage I or II follicular lymphoma were treated at The University of Texas M. D. Anderson Cancer Center. Initial staging studies included lymphangiography in 87% of the patients, computerized tomography of the abdomen and pelvis in 60%, bone marrow biopsy in 98%, and diagnostic or staging laparotomy in 33%. Forty-five patients were treated with regional radiotherapy, 84 patients with combined chemotherapy and radiotherapy, and 15 patients were treated with chemotherapy alone. RESULTS: With a median follow-up of 8.7 years (range, 48-182 months) the actuarial survival rates at 5, 10, and 15 years were 81, 69, and 63%, respectively. The freedom from relapse (FFR) rates were 66, 56, and 46%, respectively. The FFR rate was better for patients treated with chemotherapy-radiotherapy than for patients treated with radiotherapy alone (63 vs. 35% at 15 years). In addition, there were no relapses after 7.5 years in patients treated with chemotherapy-radiotherapy, but relapses continued even beyond 15 years in patients treated with radiotherapy alone. Univariate analysis for each of the treatment groups revealed age to be the only significant prognostic factor. There was no significant difference in survival or disease free survival rates for the three histologic subtypes of follicular lymphoma. CONCLUSION: The addition of chemotherapy to radiotherapy may have increased the probability of cure for patients with Stages I or II follicular lymphoma.

Increasing the production of generalists: a computer simulation.

BACKGROUND & OBJECTIVES: The Association of American Medical Colleges set a goal for US medical schools to produce 50% of their graduates as generalists. Methods for achieving this goal have not been established. METHODS: We developed a computer simulation to gauge the effect of interventions that could occur at five different points during medical school education. Each intervention would improve by 10% the proportion of trainees choosing a generalist career. RESULTS: Our model predicts that 24.1% of 1992 medical school graduates will ultimately become generalists. Any of the interventions we evaluated increased generalist production to the 25%-26.5% range. If class size is held constant and if a 10% annual improvement occurred in all of the other intervention points for 3 years, our model still predicts only 44.8% generalists. CONCLUSIONS: Computerized "what-if" analysis can effectively project specialty outcomes after various interventions. The best intervention increased generalist production 2.6 times more than did less effective interventions. The loss of primary care residents into subspecialty fellowships is substantial. Even if 100% of current medical graduates could be directed into family practice, internal medicine, and pediatric residencies in their current proportions, only a 43.7% generalist outcome would be achieved because of attrition of internists and pediatricians into subspecialties. Family practice is the most efficient producer of generalists but currently lacks either the capacity or the marketability to be the nation's sole supplier. More effective interventions are needed to achieve a 50% generalist outcome.

The radiologic assessment of the lymphoma patient from the standpoint of the clinician.

The characteristic radiologic and clinical features of the various types of lymphoma and Hodgkin's disease are discussed. In addition, the importance of the baseline radiologic evaluation of the patient with lymphoma as well as the process of restaging to assess response to therapy is detailed.

Tumor burden assessment and its implication for a prognostic model in advanced diffuse large-cell lymphoma.

Previously untreated adult patients who presented with advanced diffuse large-cell lymphoma (DLCL) at diagnosis were studied to identify possible prognostic factors. One hundred five patients were seen between 1974 and 1981; 45 patients were stage III and 60 patients were stage IV. All patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Stage III patients also received radiation therapy alternated with chemotherapy. Overall survival was 50% at 5 years and 43% at 8 years. Seventy-four patients achieved a complete remission (CR) and 37 are alive and disease-free with a median follow-up of 72 months. There was no difference in clinical outcome between stage III and stage IV. However, a proportional hazards model identified lactic dehydrogenase (LDH) level and tumor burden, among all clinical factors studied, as independent risk factors for survival. These two factors were also important for achievement of remission and relapse-free survival. Three distinct patient risk groups were identified with 5-year survival rates of 87%, 48%, and 20%, respectively. The measure of tumor burden proposed herein, along with LDH level, can be used for developing treatment programs, and for meaningful comparison of different treatment regimens, as well as assessment of prognosis.

New assessment of the prognostic significance of histopathology in Hodgkin's disease for laparotomy-negative stage I and stage II patients.

This paper describes preliminary radiotherapy results in 90 patients with Stage I and II Hodgkin's disease who were evaluated by laparotomy, including splenectomy, and liver and bone marrow biopsies. As a result of selection by laparotomy, the estimated five-year survival rate for these patients was 96%. No statistically significant differences were detected in the disease-free survival for patients with mixed cellularity, nodular sclerosis, and lymphocytic predominance disease. Since only one patient with lymphocytic depletion was in this series, no statement can be made regarding this rare histopathology. Patterns of new disease differed for Stage I and II patients. The major difference was that patients with nodular sclerosing Stage II presentations involving the mediastinum were at considerable risk of developing subsequent disease in the pulmonary parenchyma or the pleura. This finding, together with the demonstration that a histologic diagnosis of mixed cellularity did not carry an inferior prognosis, indicates the need for reassessment of the appropriateness of applying treatment programs based on results of lymphangiographically staged patients to Stage I and II patients evaluated by laparotomy.