NIVOLUMAB ASSOCIATED ENDOCRINE ABNORMALITIES: CHALLENGING CASES FROM A REFERENCE CLINIC.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. Antibodies directed against programmed cell death receptor 1 (PD-1) interrupt the ability of the cancerous cell to depress the immune system. Methods and results: We report three patients who developed different endocrine abnormalities after treatment with nivolumab, a monoclonal antibody directed against PD-1. First, we report a 76-year-old male presenting with generalized fat loss after treatment with nivolumab which predominantly affected his face and trunk. Second, we described the development of thyroiditis that presented with thyrotoxicosis and the expression of thyroid-stimulating hormone receptor antibodies (TRAb). Finally, we observed the emergence of adrenal insufficiency due to hypophysitis in another case. Conclusion: Although immune checkpoint inhibitors are an effective anticancer treatment modality, adverse effects are evident that can affect the endocrine system. These adverse events may relate to different endocrine systems that include the thyroid and pituitary glands. Also, acquired generalized lipodystrophy should be suspected in patients developing unusual fat loss after treatment with ICIs.

Risk factors for diabetic foot ulcers in metreleptin naïve patients with lipodystrophy.

AIM: Patients with lipodystrophy are at high risk for chronic complications of diabetes. Recently, we have reported 18 diabetic foot ulcer episodes in 9 subjects with lipodystrophy. This current study aims to determine risk factors associated with foot ulcer development in this rare disease population. METHODS: Ninety metreleptin naïve patients with diabetes registered in our national lipodystrophy database were included in this observational retrospective cohort study (9 with and 81 without foot ulcers). RESULTS: Patients with lipodystrophy developing foot ulcers had longer diabetes duration (p = 0.007), longer time since lipodystrophy diagnosis (p = 0.008), and higher HbA1c levels (p = 0.041). Insulin use was more prevalent (p = 0.003). The time from diagnosis of diabetes to first foot ulcer was shorter for patients with generalized lipodystrophy compared to partial lipodystrophy (p = 0.036). Retinopathy (p < 0.001), neuropathy (p < 0.001), peripheral artery disease (p = 0.001), and kidney failure (p = 0.003) were more commonly detected in patients with foot ulcers. Patients with foot ulcers tended to have lower leptin levels (p = 0.052). Multiple logistic regression estimated significant associations between foot ulcers and generalized lipodystrophy (OR: 40.81, 95% CI: 3.31-503.93, p = 0.004), long-term diabetes (≥ 15 years; OR: 27.07, 95% CI: 2.97-246.39, p = 0.003), and decreased eGFR (OR: 13.35, 95% CI: 1.96-90.67, p = 0.008). CONCLUSIONS: Our study identified several clinical factors associated with foot ulceration among patients with lipodystrophy and diabetes. Preventive measures and effective treatment of metabolic consequences of lipodystrophy are essential to prevent the occurrence of foot ulcers in these high-risk individuals.

An update on dapagliflozin for the treatment of heart failure.

Heart failure (HF) is a substantial source of morbidity and mortality. Several clinical trials have reported a significant HF benefit of sodium/glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. In 2019, the Food and Drug Administration (FDA) approved dapagliflozin to reduce hospitalization risk for HF in adults with type 2 diabetes and established cardiovascular disease or risk factors. Regardless of the presence of diabetes, the recent DAPA-HF study reported a significant relative risk (RR) reduction with dapagliflozin in the composite primary outcome of worsening HF or death from cardiovascular causes in patients with New York Heart Association (NYHA) class II, III or IV HF and an ejection fraction of 40%. There was a 30% RR reduction in hospitalizations for HF, 57% RR reduction in urgent HF visits, and 18% RR reduction in cardiovascular death. These results led the FDA to approve dapagliflozin in 2020 for the treatment of HF with reduced ejection fraction (NYHA class II-IV) in adults with and without type 2 diabetes. This article summarizes HF outcomes from large clinical trials of SGLT2 inhibitors and focuses on dapagliflozin's HF benefits. The review also covers potential mechanisms of HF benefit and the safety profile of dapagliflozin in patients with HF.

An overview of lipodystrophy and the role of the complement system.

The complement system is a major component of innate immunity playing essential roles in the destruction of pathogens, the clearance of apoptotic cells and immune complexes, the enhancement of phagocytosis, inflammation, and the modulation of adaptive immune responses. During the last decades, numerous studies have shown that the complement system has key functions in the biology of certain tissues. For example, complement contributes to normal brain and embryonic development and to the homeostasis of lipid metabolism. However, the complement system is subjected to the effective balance between activation-inactivation to maintain complement homeostasis and to prevent self-injury to cells or tissues. When this control is disrupted, serious pathologies eventually develop, such as C3 glomerulopathy, autoimmune conditions and infections. Another heterogeneous group of ultra-rare diseases in which complement abnormalities have been described are the lipodystrophy syndromes. These diseases are characterized by the loss of adipose tissue throughout the entire body or partially. Complement over-activation has been reported in most of the patients with acquired partial lipodystrophy (also called Barraquer-Simons Syndrome) and in some cases of the generalized variety of the disease (Lawrence Syndrome). Even so, the mechanism through which the complement system induces adipose tissue abnormalities remains unclear. This review focuses on describing the link between the complement system and certain forms of lipodystrophy. In addition, we present an overview regarding the clinical presentation, differential diagnosis, classification, and management of patients with lipodystrophy associated with complement abnormalities.

AN UNUSUAL CASE OF ACQUIRED PARTIAL LIPODYSTROPHY PRESENTING WITH ACANTHOSIS NIGRICANS.

About 250 patients with acquired partial lipodystrophy (Barraquer-Simons) syndrome have been reported so far. It is characterized by the loss of adipose tissue from the face and upper extremities, and accumulated fat in the rest of the body. The disease usually starts in females during childhood or adolescence, and usually after a febrile illness. Fat loss often comes into view in months or years. We present a 23-year-old female patient with acquired partial lipodystrophy , which is rarely seen.

Familial partial lipodystrophy linked to a novel peroxisome proliferator activator receptor -γ (PPARG) mutation, H449L: a comparison of people with this mutation and those with classic codon 482 Lamin A/C (LMNA) mutations.

AIMS: To describe the phenotype associated with a novel heterozygous missense PPARG mutation discovered in a Turkish family and to compare the fat distribution and metabolic characteristics of subjects with the peroxisome proliferator activator receptor -γ (PPARG) mutation with those of a cluster of patients with familial partial lipodystrophy with classic codon 482 Lamin A/C (LMNA) mutations. METHODS: The study involved four subjects with familial partial lipodystrophy who had a novel PPARG mutation (H449L) and six subjects with classic codon 482 LMNA mutations (R482W). RESULTS: Compared with subjects with LMNA R482W mutation, fat loss was generally less prominent in subjects with the PPARG H449L mutation. Partial fat loss was limited to the extremities, whilst truncal fat mass was preserved. The PPARG H449L mutation was associated with insulin resistance, hypertriglyceridaemia and non-alcoholic fatty liver disease in all affected subjects, but the severity was variable. Three out of four mutation carriers had overt diabetes or impaired glucose tolerance. Pioglitazone therapy in these three individuals resulted in a modest improvement in their metabolic control, and regular menstrual cycles in the two female subjects. CONCLUSIONS: We suggest that relatively modest fat loss in patients with PPARG mutations may render the recognition of the syndrome more difficult in routine clinical practice. The PPARG H449L mutation is associated with insulin resistance and metabolic complications, but their severity is variable among the affected subjects.

MEAN PLATELET VOLUME AND PLATELET FUNCTION ANALYSIS IN ACROMEGALIC PATIENTS BEFORE AND AFTER TREATMENT.

OBJECTIVE: Mean platelet volume (MPV) and platelet function analysis have been studied before in acromegaly, but the effect of treatment on both parameters has not been evaluated. We aimed to investigate MPV and platelet function analysis in acromegalic patients after six-months of treatment. METHODS: Forty patients with active acromegaly and 36 healthy subjects were included in the study. Plasma glucose and lipids, fibrinogen, GH, IGF-1 levels, MPV and platelet function analysis were measured. All patients with acromegaly were re-evaluated six months after treatment. RESULTS: Fasting blood glucose (FBG), GH, IGF-1, fibrinogen levels and MPV values were significantly higher in acromegalic group compared with the control. Platelet function was enhanced significantly (pcol-ADP: 0.002, pcolepinephrine: 0.002). After 6 months of treatment FBG, serum GH, IGF-1, fibrinogen and MPV decreased and collagen/ADP- and collagen/epinephrine-closure times (CT) were increased. Acromegalic patients that were in remission with long-acting SSA after surgery had significantly higher fibrinogen levels and MPV and decreased collagen/epinephrine-CT with respect to the controls (pfibrinogen: 0.001, pMPV: 0.026, pcol-epinephrine: 0.037). CONCLUSION: Acromegaly was associated with increased MPV and enhanced platelet activity. Although growth hormone hypersecretion was controlled by surgery and medical treatment, these parameters did not improve - indicating a still increased risk for cardiovascular events.

Increased risk of unfavorable metabolic outcome during short-term follow-up in subjects with nonfunctioning adrenal adenomas.

OBJECTIVE: To demonstrate long-term changes in the prevalence of several types of metabolic derangements in subjects with nonfunctioning adrenal adenomas. SUBJECTS AND METHODS: 273 subjects with adrenal adenomas, including 231 with nonfunctioning adenoma and 42 with subclinical Cushing's syndrome (sCS), were evaluated with respect to anthropometric and laboratory characteristics and prevalence of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, metabolic syndrome (MS), prediabetes and cardiovascular disease (CVD). Median duration was 24 months. Follow-up data of 114 participants with nonfunctioning adrenal adenomas are also presented while those of 117 were missing. Follow-up data regarding changes in anthropometric and laboratory parameters and prevalence rates of metabolic disturbances were obtained from the medical records. RESULTS: The prevalence rates for both patients with nonfunctioning adenoma and sCS were: dyslipidemia: 161 (59%), hypertension: 147 (54%), MS: 128 (47%), prediabetes: 62 (23%), T2DM: 49 (18%), and CVD: 21 (8%). Hypertension and CVD were prevalent in subjects with sCS compared to participants with nonfunctioning adenoma. In follow-up, body mass index (p = 0.005), systolic blood pressure (p < 0.001), waist circumference (p = 0.005), homeostasis model assessment (p = 0.046), high-sensitivity C-reactive protein (p = 0.023), total cholesterol (p < 0.001) and low-density lipoprotein cholesterol (p < 0.001) and prevalence of hypertension (p < 0.001), dyslipidemia (p < 0.001), prediabetes (p < 0.001) and MS (p < 0.01) significantly increased in subjects with nonfunctioning adenoma. CONCLUSION: The data showed that nonfunctioning adrenal adenomas were associated with the development or deterioration of atherosclerotic risk factors. Therefore, follow-up and management strategies should be developed to decrease atherosclerotic morbidity in those individuals.

Is there an association between non-functioning adrenal adenoma and endothelial dysfunction?

BACKGROUND AND AIM: Subtle changes in hypothalamic- pituitary-adrenal (HPA) axis of subjects with nonfunctioning adrenal adenoma may be associated with endothelial alterations. We sought to investigate endothelial function, visceral adiposity and osteoprotegerin (OPG) and interleukin- 18 (IL-18) levels in subjects with non-functioning adrenal adenomas. SUBJECTS AND METHODS: The adenoma group included 40 subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders. Twenty-two body mass index-matched controls were also enroled. The patients and control subjects underwent hormonal evaluation and assessment of anthropometric and metabolic parameters. Endothelial function was assessed with flowmediated dilatation (FMD) of the brachial artery and intima media thickness (IMT) of common carotid arteries. Visceral adipose tissue area was measured by computed tomography. Plasma OPG and serum IL-18 levels were also measured. RESULTS: When compared with healthy controls, the adenoma group had elevated systolic blood pressure, post-dexamethasone suppression test cortisol and reduced DHEAS. Visceral adipose tissue area and IMT of common carotid arteries were comparable. In the adenoma group, FMD of the brachial artery was significantly impaired and IL-18 level was significantly elevated. Visceral adipose tissue area was independently related with FMD. Homeostasis model assessment (HOMA) was the independent factor associated with visceral adipose tissue area. Cortisol, DHEAS and visceral adipose tissue area were independently associated with HOMA. CONCLUSIONS: We achieved evidence that could be attributable to endothelial alterations in subjects with non-functioning adrenal adenomas. Impaired FMD appeared to be a consequence of subtle changes in HPA axis in terms of elevated cortisol and reduced DHEAS as these conditions were known to disturb endothelial-dependent vasodilatation.

Prospective evaluation of tumor size and hormonal status in adrenal incidentalomas.

BACKGROUND: Because of the increased use of imaging interventions, more subjects have been diagnosed with adrenal incidentaloma in recent years. AIM: To evaluate the risk of mass enlargement, hormone hypersecretion and development of adrenal carcinomas during short-term followup. SUBJECTS AND METHODS: There were 317 subjects with incidentally discovered adrenal tumors in the registry. Forty subjects were excluded because of clinically overt hormone secretion at diagnosis and subjects with complete data were included in radiological (no.=150) and hormonal (no.=150) follow- up. Radiological evaluation was performed with computed tomography (CT) and/or magnetic resonance imaging (MRI). There were 143 subjects with adrenal adenomas and 7 subjects with other tumor types (cyst or myelolipoma). Median follow-up duration was 24 months. RESULTS: Increase in tumor size was detected in 25 subjects (17.4%) with adenomas and 1 subject with adrenal myelolipoma (14.3%). Decrease in tumor size was found in 7 subjects (4.8%) with adrenal adenomas. One patient was diagnosed with adrenocortical carcinoma during follow-up. In subjects with non-functioning adrenal adenoma (NFA, no.=120) or subclinical Cushing syndrome (sCS) (no.=30), no subject developed clinically overt hormone hypersecretion, while 8 (6%) subjects in the NFA group developed sCS. Tumor diameter and follow-up duration were significantly higher in subjects who developed sCS. CONCLUSION: In conclusion, we demonstrated that, despite being infrequent, adrenal tumors may increase in size, develop overt or subclinical hormone secretion or feature malignant transformation. Therefore, radiological and hormonal follow-up should be recommended to the patients. More investigations are needed for the establishment of long-term follow-up protocols.

Recurrent Cushing's syndrome after adrenal autotransplantation.

Adrenalectomy with adrenal autotransplantation used to be performed frequently for Cushing's disease in the past because of the limitations of conventional radiological techniques and the lack of adequate neurosurgical techniques. Today, however, bilateral adrenalectomy may be still required for selective patients with Cushing's syndrome when partial hypophysectomy has failed to control hypercortisolism or the source for ectopic ACTH syndrome could not be determined. Here, we report a case of recurrent Cushing's syndrome due to a pituitary adenoma, who was treated with bilateral adrenalectomy and autotransplantation for her Cushing's syndrome. Having determined pituitary adenoma as the cause of recurrent Cushing's syndrome after endocrinological investigations and imaging, we were able to treat the patient with transsphenoidal adenomectomy. We suggest that transsphenoidal resection of the adenoma rather than excision of the autotransplants and adrenal remnants should be the preferred treatment method for recurrent Cushing's disease.

Non-functioning adrenal incidentalomas are associated with elevated D-dimer levels.

AIM: Although the majority of adrenal incidentalomas (AI) are non-functioning, studies evaluating metabolic disturbances in this particular group are limited. The objective of this study is to investigate metabolic syndrome components and levels of plasma von Willebrand factor (VWF), fibrinogen, and D-dimer in subjects with non-functioning AI. SUBJECTS AND METHODS: Forty-five subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders and 37 healthy controls were enrolled. The patients and controls underwent hormonal evaluation including morning cortisol, ACTH, post-dexamethasone suppression test (DST), morning cortisol, DHEAS, and urinary free cortisol. Anthropometric and metabolic parameters and body composition were assessed and fibrinogen, D-dimer, and VWF were measured. RESULTS: When compared with healthy controls, subjects with AI had significant elevations in several metabolic and anthropometric parameters, uric acid, post-DST cortisol, and D-dimer. When compared with body mass index-matched controls, blood pressure (p=0.004), uric acid (p=0.009), post-DST cortisol (p=0.014), and D-dimer (p=0.045) remained significantly elevated. We demonstrated weak correlations between D-dimer and other metabolic and anthropometric variables. Morning cortisol was demonstrated as an independent variable associated with homeostasis model assessment levels in subjects with AI (beta=410, p=0.004). CONCLUSION: Individuals with clinically and hormonally inactive adrenal adenomas feature insulin resistance and a variety of metabolic disturbances. The subtle cortisol autonomy seems to be associated with insulin-resistant state. D-dimer elevation in AI group was a consequence of insulin-resistant state associated with subtle cortisol autonomy rather than a direct effect of cortisol secretion.

Reduction of major amputations after starting a multidisciplinary diabetic foot care team: single centre experience from Turkey.

INTRODUCTION: It is widely recognized that a multidisciplinary team is effective in the management of diabetic foot ulcers. Contrary to developed countries, multidisciplinary diabetic foot care teams and/or clinics have not been constructed in most centres in developing countries. The aim of this study was to present our data regarding amputation rates and profiles before and after starting the Dokuz Eylul University multidisciplinary diabetic foot care team. METHODS: This study includes data from diabetic foot ulcer episodes which were managed in Dokuz Eylul University Hospital between January 1999 and January 2008. The data was collected prospectively during a minimum follow-up of 6 months in all ulcers. After January 2002, management of ulcers was coordinated by the diabetic foot care team (n=437). Amputation rates were compared to those who were admitted before January 2002 (n=137). RESULTS: Overall amputation and minor amputation rates were similar for both periods. However, major amputations were observed to be decreased after starting the Dokuz Eylul University multidisciplinary diabetic foot care team (20.4% vs. 12.6%, p=0.026). CONCLUSIONS: Our results demonstrated that major amputation rates can be reduced by team work. Formation of multidisciplinary diabetic foot care teams and clinics should be encouraged in Turkey.

Hypercalcemia of primary hyperparathyroidism was treated by cinacalcet in a patient with liver cirrhosis.

Cinacalcet is a type II calcimimetic agent which is an allosteric modulator of the calcium-sensing receptor (CaR) located on the surface of the parathyroid cells. Cinacalcet increases the sensitivity of CaR via binding to the transmembrane region of CaR. Increasing sensitivity of CaR causes reduced secretion of parathyroid hormone (PTH) and suppression of serum calcium levels. Cinacalcet has recently been approved by Federal Drug Administration (FDA) for the treatment of patients with secondary hyperparathyroidism on maintenance dialysis and hypercalcemia in patients with parathyroid cancer. It is used also in Europe for both indications. Several controlled studies have shown that cinacalcet is effective in normalizing serum calcium levels also in primary hyperparathyroidism. Cinacalcet is metabolized primarily in the liver by N-dealkylation leading to carboxylic acid and oxidation of naphthalene ring to form dihydrodiols. The safety and optimal dosage of the drug in hypercalcemic patients with liver impairment remains unclear. We present a patient with Child-Pugh B class primary biliary cirrhosis who presented with moderate hypercalcemia and was diagnosed as primary hyperparathyroidism. As she refused having parathyroid surgery for her parathyroid adenoma at first, her hypercalcemia was treated successfully with 30 mg/day cinacalcet for 6 months. Cinacalcet was discontinued after 6 months. Her calcium level increased gradually. As she accepted surgery this time, her parathyroid adenoma was removed by minimally invasive parathyroidectomy. Parathyroid adenoma was confirmed pathologically. Her calcium levels maintained within the normal ranges after surgery.

A case of Gitelman's syndrome presenting with extreme hypokalaemia and paralysis.

Gitelman's syndrome is an autosomal recessive disorder caused by various mutations of the thiazide- sensitive sodium chloride cotransporter gene. Hypokalaemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria are major clinical features of the syndrome. The onset of the disease is in early adulthood with a mild muscle weakness complaint or incidentally diagnosed hypokalaemia by blood test. However, it has a significant impact on quality of life of patients. Rarely, patients with Gitelman's syndrome may present with hypokalaemic paralysis. Profound hypokalaemia is uncommon in Gitelman's syndrome. Here we report a case of Gitelman's syndrome, who presented with hypokalaemic paralysis and extreme hypokalaemia. To the best of our knowledge, after a Medline search, this is the most severe hypokalaemia described in a patient with Gitelman's syndrome.

Plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor levels in non-alcoholic steatohepatitis.

AIM: This study was conducted to demonstrate the plasminogen activator inhibitor- 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor antigen (TAFI-Ag) levels in non-alcoholic steatohepatitis (NASH). MATERIALS AND METHODS: Twenty-seven patients with biopsy-proven NASH and 18 healthy controls (HC) were recruited for the study. Anthropometric data, liver histology (no.=20) and laboratory parameters including PAI-1 and TAFI-Ag assessments were recorded. RESULTS: When compared with HC, patients with NASH had higher body weight, higher waist circumference, elevated blood pressure, higher fasting plasma glucose (FPG) levels and higher homeostasis model assessment (HOMA) scores. The mean plasma PAI-1 levels of patients was found to be higher than HC (87.60 ng/ml vs 30.84 ng/ml p=0.000) and mean plasma TAFI-Ag levels of patients was found to be significantly lower (8.69 microg/ml vs 12.19 microg/ml p=0.000). PAI-1 levels were correlated with systolic blood pressure, age, body weight, transaminases, waist circumference, FPG, body mass index, and HOMA score. TAFI-Ag levels were found to be negatively correlated with transaminases, waist circumference, and body weight. In multiple regression analysis, BMI was the independent variable effecting PAI-1 levels. We did not show any association between PAI-1, TAFI-Ag, disease activity score and fibrosis score. HOMA was the independent variable effecting liver fibrosis in our patients. CONCLUSION: In this study we demonstrated that patients with biopsy-proven NASH had higher PAI-1 and lower TAFI-Ag expression than HC. Elevated levels of PAI-1 in NASH is the consequence of insulin resistance state. Lower TAFI-Ag levels may be related to the overactivation of TAFI pathway resulting in TAFI-Ag depletion. Furthermore, liver function disturbances may impair TAFI production in NASH. We also showed that NASH patients even with slight elevations of transaminases feature marked insulin resistance and components of metabolic syndrome.

Low transforming growth factor-beta1 serum levels in idiopathic male osteoporosis.

INTRODUCTION: Although the etiology of osteoporosis is different between men and women, the underlying pathophysiological mechanism is similar, namely an absolute or relative increase in bone resorption, leading to progressive bone loss. Transforming growth factor (TGF)-beta1 is a growth factor in human bone, which is produced by osteoblasts, and which has various effects on osteoclasts and osteoblasts. The aim of our study was to determine serum TGF-beta1 levels in male patients with idiopathic osteoporosis. METHODS: Twenty five males with idiopathic osteoporosis and 25 age-matched controls were studied. Osteoporosis was defined by a T score of <-2.5 in the lumbar spine or at the femoral neck. We measured levels of TGF-beta1, estradiol, total and bioactive testosterone. Various markers of bone remodeling were also measured. RESULTS: TGF-beta1 was significantly lower in osteoporotic patients than in controls (3.706 ng/dl, 25-75 percentiles: 2.81-5.33 vs 8.659 ng/dl, 25-75 percentiles: 4.837-11.835; p=0.000). Moreover, TGF-beta1 levels were positively correlated with bone mineral density (BMD) at the femoral neck (r=0.439, p=0.028), and at the lumbar spine (r=0.41, p=0.042). No correlation was found between serum estradiol, testosterone and TGF-beta1 levels. DISCUSSION: Serum TGF-beta1 levels are depressed in osteoporotic men and are positively correlated with hip and spine BMD. The results of our study suggest that TGF-beta1 may play a role in the pathogenesis of idiopathic male osteoporosis.

Frequency and severity of musculoskeletal symptoms in humans during an outbreak of trichinellosis caused by Trichinella britovi.

Musculoskeletal symptoms such as myalgia are well-known features in the course of trichinellosis; however, the characteristics of musculoskeletal findings have been described in detail in only 1 study. The present study was aimed to determine the joint and muscle symptoms in subjects diagnosed with acute trichinellosis at our rheumatology unit during a Trichinella britovi outbreak that occurred in Izmir, Turkey, in 2004. In total, 98 patients (55 females, 43 males; mean age 32.3 +/- 10.9 yr) were included in the study. A detailed history and full musculoskeletal examination were obtained in each patient. A self-administered questionnaire developed for recording the musculoskeletal symptoms was completed monthly until all the symptoms were resolved. Pain at the joints, restriction of movements (in shoulders, elbows, wrists, knees, ankles, and temporomandibular joints), myalgia, and muscle weakness (neck and shoulder girdle, muscles of the upper and forearm, back, thigh, and calf muscles) were assessed in every patient. Eosinophil counts, serum levels of creatine kinase, and lactate dehydrogenase also were analyzed. The most frequent musculoskeletal symptoms were muscle pain (86 cases [87.8%]), joint pain (83 [84.7%]), subjective muscle weakness (75 [76.5%]), and restriction of joint movements (63 [64.3%]). Calves, upper arm, neck and shoulder girdle, and forearms were the most affected muscle groups. Muscle pain was reported more frequently in the upper than in the lower extremities and during activity. The most frequent painful joints were shoulders, knees, wrists, and ankles. Upper extremity joints were affected more frequently than the lower extremity joints (77.6 vs. 70.4%). Joint pain occurred more frequently at rest. Both muscle weakness and restriction of joint movements were reported in and around the most frequently affected regions. No evidence of arthritis and objective muscle weakness was noted on physical examination in any patient. Musculoskeletal symptoms in the course of T. britovi infection are frequent but with an excellent prognosis. Joint pain in people suffering from acute trichinellosis may occur more frequently than reported previously.

Hydroxyurea associated leg ulcer succesfully treated with hyperbaric oxygen in a diabetic patient.

Oxygen tension in healing tissues is heterogeneous. Increased oxygen mostly stimulates repair mechanisms and enhances tissue healing. Hyperbaric oxygen therapy increases blood and tissue oxygen content and may help maintain cellular integrity and function. Hydroxyurea (HU) is a cytotoxic agent, which leads to inactivation of ribonucleotide reductase, inhibition of cellular DNA synthesis, and cell death in the S phase. HU induced leg ulcers occur after use of this agent for a long time and at higher cumulative doses. Here we describe a diabetic patient with foot ulcer associated with HU treatment for polycythemia vera, who was treated successfully with hyperbaric oxygen and general wound care after discontinuation of HU. Faster improvement of leg ulcer in our patient compared to literature regarding HU withdrawal as single therapy suggests that hyperbaric oxygen may be helpful in the management of HU associated leg ulcers, especially in diabetic subjects.