Spatial distribution and determinants of tuberculosis incidence in Mozambique: A nationwide Bayesian disease mapping study.

INTRODUCTION: Mozambique is a high-burden country for tuberculosis (TB). International studies show that TB is a disease that tends to cluster in specific regions, and different risk factors (HIV prevalence, migration, overcrowding, poverty, house condition, temperature, altitude, undernutrition, urbanization, and inadequate access to TB diagnosis and treatment) are reported in the literature to be associated with TB incidence. Although Mozambique has a higher burden of TB, the spatial distribution, and determinants of TB incidence at the sub-national level have not been studied yet for the whole country. Therefore, we aimed to analyze the spatial distribution and determinants of tuberculosis incidence across all 154 districts of Mozambique and identify the hotspot areas. METHOD: We conducted an ecological study with the district as our unit of analysis, where we included all cases of tuberculosis diagnosed in Mozambique between 2016 and 2020. We obtained the data from the Mozambique Ministry of Health and other publicly available open sources. The predictor variables were selected based on the literature review and data availability at the district level in Mozambique. The parameters were estimated through Bayesian hierarchical Poisson regression models using Markov Chain Monte Carlo simulation. RESULTS: A total of 512 877 people were diagnosed with tuberculosis in Mozambique during our five-year study period. We found high variability in the spatial distribution of tuberculosis incidence across the country. Sixty-two districts out of 154 were identified as hotspot areas. The districts with the highest incidence rate were concentrated in the south and the country's central regions. In contrast, those with lower incidence rates were mainly in the north. In the multivariate analysis, we found that TB incidence was positively associated with the prevalence of HIV (RR: 1.23; 95 % CrI 1.13 to 1.34) and negatively associated with the annual average temperature (RR: 0.83; 95 % CrI 0.74 to 0.94). CONCLUSION: The incidence of tuberculosis is unevenly distributed across the country. Lower average temperature and high HIV prevalence seem to increase TB incidence. Targeting interventions in higher-risk areas and strengthening collaboration between HIV and TB programs is paramount to ending tuberculosis in Mozambique, as established by the WHO's End TB strategy and the Sustainable Development Goals.

Predictors of early and long-term mortality after ICU discharge in critically ill COVID-19 patients: A prospective cohort study.

BACKGROUND: To mitigate mortality among critically ill COVID-19 patients, both during their Intensive Care Unit (ICU) stay and following ICU discharge, it is crucial to measure its frequency, identify predictors and to establish an appropriate post-ICU follow-up strategy. METHODS: In this multicentre, prospective cohort study, we included 586 critically ill COVID-19 patients. RESULTS: We observed an overall ICU mortality of 20.1% [95%CI: 17.1% to 23.6%] (118/586) and an overall hospital mortality of 25.4% [95%CI: 22.1% to 29.1%] (149/586). For ICU survivors, 30 days (early) post-ICU mortality was 5.3% [95%CI: 3.6% to 7.8%] (25/468) and one-year (late) post-ICU mortality was 7.9% [95%CI: 5.8% to 10.8%] (37/468). Pre-existing conditions/comorbidities were identified as the main independent predictors of mortality after ICU discharge: hypertension and heart failure were independent predictors of early mortality; and hypertension, chronic kidney disease, chronic obstructive pulmonary disease and cancer were independent predictors of late mortality. CONCLUSION: Early and late post-ICU mortality exhibited an initial surge (in the first 30 days post-ICU) followed by a subsequent decline over time. Close monitoring of critically ill COVID-19 post-ICU survivors, especially those with pre-existing conditions, is crucial to prevent adverse outcomes, reduce mortality and to establish an appropriate follow-up strategy.

Aseptic Pustulosis of the Folds Successfully Treated with Methotrexate.

An otherwise healthy 47-year-old woman presented with confluent pustular lesions on the scalp for 5 months and asymptomatic pustular lesions on the trunk and extremities for 2 weeks. She did not have systemic clinical manifestations and was treated with oral antifungals and antibiotics (amoxicillin, and clavulanic acid and flucloxacillin), with no effect. The lesions were unrelated to her menstrual cycle, and she had no history of dermatosis, including acne, psoriasis, or folliculitis. (SKINmed. 2022;20:466-468).

Prevalence of rheumatoid arthritis in South America: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) is among the most prevalent chronic autoimmune and inflammatory diseases worldwide. The aim of this study was to establish a pooled estimate of the RA prevalence in South America by means of a meta-analysis of the available epidemiologic studies. Systematic searches in PubMed, Lilacs, SciELO, Scopus, and Web of Science databases (updated May 2019) were done followed by a systematic grey literature search to identify original research articles and reports, published after 2000, providing data of RA prevalence in any South American country. Proportion meta-analysis of weighted pooled was performed, with between-trial heterogeneity assessed by the inconsistency relative index. Sensitivity analyses and sub-group analyses were also done. A total of 25 articles, representing 27 population-based studies were included. Pooled prevalence of RA resulted in 0.48% with 591,981 cases in a population of 114,537,812 individuals (I2=99%). Brazil and Colombia presented the lowest rates of RA prevalence 0.22%, and 0.24%, respectively. RA prevalence in indigenous population was higher 1.45%, and studies using COPCORD method reported also the highest rates 1.07%.

Prevalence of rheumatoid arthritis in South America: a systematic review and meta-analysis / Prevalência da artrite reumatoide na América do Sul: revisão sistemática e meta-análise

Abstract Rheumatoid arthritis (RA) is among the most prevalent chronic autoimmune and inflammatory diseases worldwide. The aim of this study was to establish a pooled estimate of the RA prevalence in South America by means of a meta-analysis of the available epidemiologic studies. Systematic searches in PubMed, Lilacs, SciELO, Scopus, and Web of Science databases (updated May 2019) were done followed by a systematic grey literature search to identify original research articles and reports, published after 2000, providing data of RA prevalence in any South American country. Proportion meta-analysis of weighted pooled was performed, with between-trial heterogeneity assessed by the inconsistency relative index. Sensitivity analyses and sub-group analyses were also done. A total of 25 articles, representing 27 population-based studies were included. Pooled prevalence of RA resulted in 0.48% with 591,981 cases in a population of 114,537,812 individuals (I2=99%). Brazil and Colombia presented the lowest rates of RA prevalence 0.22%, and 0.24%, respectively. RA prevalence in indigenous population was higher 1.45%, and studies using COPCORD method reported also the highest rates 1.07%.

Resumo A artrite reumatóide (AR) está entre as doenças autoimunes e inflamatórias crônicas mais prevalentes no mundo. O objetivo deste estudo foi estabelecer uma estimativa conjunta da prevalência da AR na América do Sul por meio de uma meta-análise dos estudos epidemiológicos disponíveis. Buscas sistemáticas nas bases de dados PubMed, Lilacs, SciELO, Scopus e Web of Science (atualizado em maio de 2019) foram seguidas por uma busca sistemática na literatura cinzenta para identificar artigos e relatórios de pesquisa originais, publicados após 2000, fornecendo dados de prevalência de AR em qualquer país da América do Sul. Foi realizada uma meta-análise da proporção de dados agrupados ponderados, com heterogeneidade entre experimentos avaliada pelo índice relativo de inconsistência. Análises de sensibilidade e de subgrupos também foram realizadas. Foram incluídos um total de 25 artigos, representando 27 estudos de base populacional. A prevalência agrupada de AR resultou em 0,48% com 591.981 casos em uma população de 114.537.812 indivíduos (I2=99%). Brasil e Colômbia apresentaram as menores taxas de prevalência de AR 0,22% e 0,24%, respectivamente. A prevalência da AR na população indígena foi maior 1,45%, e estudos pelo método COPCORD relataram também as maiores taxas 1,07%.

Implications of a defined daily dose fixed database for drug utilization research studies: The case of statins in Portugal.

AIMS: Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. METHODS: The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDDYEAR ) and by the DDD last-year approach (DDDLAST ). PDDs were calculated according to the year-by-year approach (PDDYEAR ). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDDYEAR and DDDYEAR units. RESULTS: The DDDYEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDDLAST and PDDYEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDDYEAR /1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009. CONCLUSIONS: A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies.

Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas.

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients' risk stratification.

Vasculitic Leg Ulcer Revealing an Essential Thrombocythemia.

A 64-year-old man was referred to our department due to painful ulcers on the right leg that had evolved over the previous 6 months. There was also progressive weight loss. He had no relevant medical history. Clinically, we observed multiple ulcers, some of them with a necrotic base, located over the medial malleolus and calcaneus (Figures 1 and 2), with an associated livedoid appearance of the dorsum of the feet. A skin biopsy revealed epidermis with ulceration. The superficial and deep dermis showed perivascular and interstitial neutrophilic inflammatory infiltrate, with fibrinoid necrosis of the vessels as well as leukocytoclasia (Figure 3). Blood analysis showed significant thrombocytosis (1128×106 per µL) and leukocytosis (21.38×106 per µL). The autoimmune study showed no abnormalities. Abdominal ultrasound showed hepatosplenomegaly. The patient was seen in the hematology department, and a bone marrow biopsy was obtained that was compatible with essential thrombocythemia (ET). The patient had a karyotype that showed no metaphases, and was BCR-ABL-negative and JAK2-positive. He started treatment with α-interferon 1.8 million units, three times per week. Daily polyacrylate wound dressing was carried out to debride the skin lesions, and there was gradual improvement of the ulcers (Figure 4).

EGFR Inhibitors-related Panniculitis: A New Side Effect.

Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of advanced malignancies, and their skin toxicity is frequent and well recognized in the literature. We report the case of a 69-year-old patient with a history of adenocarcinoma of the lung treated with several EGFR inhibitors and the development of skin lesions compatible with panniculitis. The reproducibility of the lesions with different inhibitors reinforces the causal relationship with the drug, representing the first report in the literature of this side effect.

Perianal purpuric plaques revealing an amyloid light-chain amyloidosis: case report and review of the literature.

Systemic immunoglobulin light chain amyloidosis is the most common and severe type of amyloidosis. There is an abnormal fibrillary protein deposition in tissues that leads to progressive and irreversible organ dysfunction. The most commonly affected organs are kidney and heart. Although rare, cutaneous manifestations may be the first clinical sign of the disease and usually present as hemorrhagic lesions, such as purpura, petechiae, and ecchymosis. We present a 71-year-old man that presented to our department because of exuberant purpuric plaques in the anogenital area as the first manifestation of an amyloid light-chain (AL) amyloidosis. The multi-organ involvement in addition to rapid clinical deterioration precipitated the patient's death four months later.

TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Telomerase reverse transcriptase gene (TERT) promoter (TERTp) mutations have been reported as potential predictors of poor prognosis in several cancers, but the prognostic value of TERTp mutations for cutaneous squamous cell carcinoma (cSCC) has not been determined. OBJECTIVE: To evaluate the frequency of TERTp mutations and correlate it with clinicopathologic features and patient outcome. METHODS: We performed genetic profiling of TERTp mutations in a retrospective series of cSCCs. The predictive value of TERTp mutations and clinicopathologic parameters were assessed by using logistic regression models. RESULTS: A total of 152 cSCCs from 122 patients were analyzed for TERTp mutations; the mutation rate was 31.6% (48 of 152), and it was higher in invasive cSCC (42 of 121 [34.7%]) than in in situ cSCC (6 of 31 [19.4%]). Age older than 75 years (odds ratio [OR], 14.84; P = .013] and TERTp mutation (OR, 8.11; P = .002) were independent predictors of local recurrence. TERTp mutation (OR, 15.89; P = .022) was independently associated with higher risk of lymph node metastasis. LIMITATIONS: The restricted number of metastatic cases. CONCLUSION: TERTp mutations may prove to be a molecular biomarker with prognostic significance in invasive cSCC, but larger studies are needed.

Pemphigoid gestationis successfully treated with intravenous immunoglobulin.

Pemphigoid gestationis (PG), also known as herpes gestationis, is a rare autoimmune blistering disease specific to pregnancy, which usually presents in the second or third trimesters and, in 15%-25% of cases, during the immediate postpartum period.1Although the ethiopathogeny of PG is not fully clarified, most patients develop antibodies against a 180 kDa transmembrane hemidesmosomal protein (BP180; BPAG2; collagen XVII).2 PG has a strong association with human leucocyte antigens DR3 and DR4.3We report a case of a 29-year-old female patient with PG successfully treated with intravenous immunoglobulin.

SDHD promoter mutations are rare events in cutaneous melanomas but SDHD protein expression is downregulated in advanced cutaneous melanoma.

BACKGROUND: SDHD promoter mutations were reported in 4-10% of cutaneous melanomas. The advanced clinico-pathological and patient survival association with SDHD mutation and/or expression in cutaneous melanoma remains controversial. OBJECTIVES: To evaluate the presence of SDHD promoter mutations and SDHD protein expression in a melanoma series and its possible association with prognosis and survival of the patients. METHODS: We assessed SDHD promoter status in cutaneous melanomas (CM), ocular melanomas (OM) and melanoma cell lines, and the expression of SDHD protein by immunohistochemistry in CM and OM, and by western blot in melanoma cell lines. We explored the putative association between SDHD protein expression and clinico-pathological and prognostic parameters of melanoma. RESULTS: We detected 2% of SDHD promoter mutations in CM, but none in OM and cell lines. SDHD protein expression was present in all CM, in OM and in all CM and OM derived cell lines analysed. A significant association between lower SDHD mean protein expression and presence of ulceration and higher pT stage was found. CONCLUSIONS: SDHD promoter mutation seems to be a rare event in CM but SDHD lower expression might associate with worst prognostic features in CM.

GATA3 and MYB Expression in Cutaneous Adnexal Neoplasms.

Knowledge of staining pattern of certain immunostains might be useful in the classification of cutaneous adnexal tumors that can have clinical importance. We studied GATA3 and MYB expression in archival materials of 220 adnexal tumors comprised of sebaceous carcinomas, follicular tumors, apocrine carcinoma, predominantly apocrine tumors, predominantly eccrine tumors, and others including adenoid cystic carcinomas. Nuclear GATA3 expression was seen in 70% (153/220) of cases, including sebaceous carcinoma (93%), apocrine carcinoma (93%), follicular neoplasms (100%), and predominantly apocrine neoplasms (69%), yet only 38% of predominantly eccrine neoplasms. Nuclear MYB expression was seen in 43% (81/188) of cases, including adenoid cystic carcinoma (90%), predominantly apocrine tumors (66%), follicular neoplasms (49%), apocrine carcinomas (14%), predominantly eccrine tumors (11%), and sebaceous carcinomas (4%). GATA3 and MYB expression were noted in 43% (9/21) and 24% (5/21) of cutaneous metastases, respectively. Expression of both GATA3 and MYB was noted in 33% (60/184) of primary adnexal tumors versus 19% (4/21) of cutaneous metastases. GATA3 preferentially labels tumors with follicular, sebaceous, and apocrine differentiation. MYB is potentially a helpful stain in the distinction of desmoplastic trichoepithelioma versus basal cell carcinoma. The coexpression of GATA3 and MYB might be helpful in the distinction of primary cutaneous adnexal carcinoma versus metastatic breast, salivary gland, or urothelial carcinoma.

Glycogenic hepatopathy in young adults: a case series

Glycogenic hepatopathy is a rare and underecognized complication in long-standing poorly controlled type 1 diabetes mellitus patients. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics, such as nonalcoholic fatty liver disease. Glycogenic hepatopathy is characterized by the combination of poorly controlled diabetes, acute liver injury with marked elevation in serum aminotransferases, and the characteristic histological features on liver biopsy. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control. In this report, we describe four cases of adult patients presenting elevated serum transaminases and hepatomegaly with a history of poorly controlled type I diabetes mellitus. One of the patients had also elevated amylase and lipase in the serum, without clinical or imagiologic evidence of acute pancreatitis. Liver biopsy was performed in all patients and revealed glycogenic hepatopathy. Clinician’s awareness of glycogenic hepatopathy should prevent diagnostic delay or misdiagnosis and will provide better insight and management for this condition (AU)

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Cutaneous Richter Syndrome mimicking a lower limb cellulitis infection - a case report and review of the literature.

Richter syndrome (RS) is characterized by the development of a high-grade lymphoma in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Herein, we present the case of an 85-year-old woman with a 3-year history of stable asymptomatic CLL that developed a cutaneous RS. The patient presented with painless inflammation in the left leg and foot that was initially diagnosed as a cellulitis infection. She was treated accordingly with ceftriaxone and clindamycin. However, after completing the antibiotic regimen, not only did the inflammation persist, but also superimposed painless nodules gradually appeared on the left leg and foot over the course of four months. The histopathological examination of the nodules revealed a large B-cell cutaneous lymphoma. The patient underwent chemotherapy with CVP, followed by R-CHOP, resulting in a reduction of size of the nodules and remission of the inflammation. The patient died five months after the diagnosis owing to a bacterial pneumonia. We identified in previous reports a total of fifteen cases of cutaneous RS. Most cases presented with rapidly growing tumors or multiple erythematous nodules, similar to our case. This case of a cutaneous RS mimicking a cellulitis infection underlines the importance of a low threshold for performing biopsies of suspicious skin lesions in patients with CLL/SLL.

Glycogenic hepatopathy in young adults: a case series.

Glycogenic hepatopathy is a rare and under-recognized complication in long-standing poorly controlled type 1 diabetes mellitus patients. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics, such as nonalcoholic fatty liver disease. Glycogenic hepatopathy is characterized by the combination of poorly controlled diabetes, acute liver injury with marked elevation in serum aminotransferases, and the characteristic histological features on liver biopsy. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control. In this report, we describe four cases of adult patients presenting elevated serum transaminases and hepatomegaly with a history of poorly controlled type I diabetes mellitus. One of the patients had also elevated amylase and lipase in the serum, without clinical or imagiologic evidence of acute pancreatitis (AP). Liver biopsy was performed in all patients and revealed glycogenic hepatopathy. Clinician's awareness of glycogenic hepatopathy should prevent diagnostic delay or misdiagnosis and will provide better insight and management for this condition.

Overexpression of pyruvate dehydrogenase kinase supports dichloroacetate as a candidate for cutaneous melanoma therapy.

OBJECTIVE: We aimed to verify if there is evidence to consider dichloroacetate (DCA), which inhibits the pyruvate dehydrogenase kinase (PDK) and reverts the metabolic shift of cancer cells from glycolysis to oxidative phosphorylation, as a promising drug for therapy of cutaneous melanoma (CM) patients. RESEARCH DESIGN AND METHODS: We assessed the expression profile of PDK 1, 2 and 3 in a series of melanoma samples, to verify if melanoma tumors express the DCA targets, if this expression correlates with the activation of important signaling cascades for melanomagenesis and also with the prognosis of melanoma patients. We also established the sensitivity of melanoma cell lines to DCA treatment, by assessing their metabolic alterations, proliferation and survival. RESULTS: We observed that both PDK 1 and 2 isoforms are overexpressed in CM compared to nevi, this expression being associated with the expression of the mTOR pathway effectors and independent of the BRAF mutational status. Melanoma cell lines treated with DCA showed a shift in metabolism, that is, a decrease in glucose consumption and lactate production, downregulation of proliferation, an increase of apoptosis and a decrease in mTOR pathway activation. CONCLUSION: Our results suggest that PDK expression may play a role in melanoma development and that DCA can be useful for CM therapy, alone or in combination with mTOR inhibitors.