Incidence and characteristics of Lyme neuroborreliosis in adult patients with facial palsy in an endemic area in the Netherlands.

Making a distinction between facial palsy due to Lyme neuroborreliosis (LNB) and idiopathic facial palsy (IFP) is of importance to ensure timely and adequate treatment. The study objective was to assess incidence and patient characteristics of facial palsy due to LNB. Hospital records were reviewed of adult patients with facial palsy visiting the departments of neurology and/or otorhinolaryngology of Gelre hospitals between June 2007 and December 2017. Gelre hospitals are located in an area endemic for Lyme borreliosis. Patients with LNB had pleocytosis and intrathecal antibody production or pleocytosis with positive IgG serology. Patients with IFP had negative serology. Clinical characteristics were compared between patients with LNB and patients with IFP. Five hundred and fifty-nine patients presented with facial palsy, 4.7% (26) had LNB and 39.4% (220) IFP. The incidence of facial palsy due to LNB was 0.9/100 000 inhabitants/year. Over 70% of patients with facial palsy due to LNB did not report a recent tick bite and/or erythema migrans (EM). Patients with facial palsy due to LNB presented more often in July to September (69.2% vs. 21.9%, P < 0.001), and had more often headache (42.3% vs. 15.5%, P < 0.01). To reduce the risk of underdiagnosing LNB in an endemic area, we recommend testing for LNB in patients with facial palsy in summer months especially when presenting with headache, irrespective of a recent tick bite and/or EM.

Laser therapy for onychomycosis in patients with diabetes at risk for foot ulcers: a randomized, quadruple-blind, sham-controlled trial (LASER-1).

BACKGROUND: Patients with diabetes mellitus are at high risk for onychomycosis, which is related to the development of foot ulcers. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the treatment of onychomycosis with local laser therapy. METHODS: In a single-centre, randomized (1:1), quadruple-blind, sham-controlled trial, patients and microbiological confirmation with diabetes mellitus, at risk for developing diabetic foot ulcers (Sims classification score 1, 2) and a clinical suspicion on onychomycosis, were randomized to either four sessions neodymium-doped yttrium aluminium garnet (Nd-YAG) 1064 nm laser or sham treatment. The primary outcome was clinical and microbiological cure of onychomycosis after 1-year follow-up. RESULTS: From March 2015 to July 2016, 64 patients were randomized; 63 could be analysed. Trichophyton rubrum was the most detected pathogen. There was no difference in the primary outcome between laser and sham treatment. With the exception of a subungual haematoma in the fifth toenail occurring 2 weeks after laser treatment, the results suggested that treatment with Nd-YAG 1064 nm laser is safe. CONCLUSION: At this moment, there is no evidence of any effect of laser treatment for onychomycosis in patients with diabetes at increased risk for foot ulcers, at least not within 1 year after treatment.

Is orthostatic hypotension related to falling? A meta-analysis of individual patient data of prospective observational studies.

Background: orthostatic hypotension (OH) is one out of many risk factors believed to contribute to an increased fall risk in elderly subjects but it is unclear whether an independent association between OH and falling exists. Objectives: to perform an individual patient data (IPD) meta-analysis of prospective observational studies investigating the relationship between OH and falling. Design: MEDLINE, EMBASE, the Cochrane Library and the abstracts of annual meetings of selected hypertension societies were searched. Both one-stage (analysing all IPD from all studies simultaneously) and two-stage (analysing IPD per study, and then pooling the results) methods were used, and both logistic and cox regression analyses were performed. The study protocol was published on PROSPERO (2015:CRD42015019178). Results: from 34 selected abstracts, 6 studies were included. IPD were provided in 1,022 patients from 3 cohorts and were included in the IPD meta-analysis. The one-stage meta-analysis showed a significant relationship between OH and time to first fall incident (hazard ratio (HR) 1.52 (95% Confidence Interval (CI) 1.23-1.88)). No significant relationship between OH and falling was found in the one-stage logistic regression analysis and the two-stage logistic and cox regression analyses. Conclusions: this IPD meta-analysis of prospective observational studies showed a clear and significant relationship between OH and time to first fall incident. Although the ORs of falling was not significantly different for patients with and without OH, a the cox regression analyses reporting HRs and including time to incident provided more clinically relevant information in present meta-analysis.

Time for considering other blood pressure target values in elderly patients with type 2 diabetes?

Although blood pressure control has undoubtedly proven its benefits in reducing the high cardiovascular risk in patients with type 2 diabetes mellitus (T2DM), it still remains unclear whether intensive antihypertensive treatment in old age (> 75 years) is beneficial. Many of the current guidelines recommend a systolic blood pressure (SBP) < 140 mmHg or lower, unless patients are at high risk for possible adverse events such as postural hypotension (1,2). This perspective aims to get a discussion started on the appropriate target SBP value for patients with T2DM aged older than 75 years.We would like to propose the less stringent value of< 160 mmHg in this specific population.

Eosinophils may predict occult lymph node metastasis in early oral cancer.

OBJECTIVE: The aim of this study was to investigate whether tumor-associated tissue eosinophilia (TATE) in early oral squamous cell carcinoma (OSCC) would aid in predicting occult lymph node metastasis. PATIENTS AND METHODS: Seventy-one patients undergoing elective neck dissection for T1 and T2 OSCC were evaluated for clinical features, prognosis, and TATE. The degree of TATE in OSCC was statistically analyzed in relation to the clinicopathological features, tumor invasion, occult lymph node metastasis, and survival using χ(2) test and Kaplan-Meier method. RESULTS: Statistical analysis revealed that intense TATE was a significant feature (p = 0.004) to predict occult lymph node metastasis in patients with early OSCC. All regional recurrences of the OSCC occurred in patients showing intense TATE. CONCLUSIONS: These results suggest that intense TATE can be clinically used as a predictive factor for occult lymph node metastasis. CLINICAL RELEVANCE: The presence of intense TATE is an adjunctive histopathological marker to reinforce the indication of elective neck dissection of the patients with early OSCC.

Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

Glycaemic control and the risk of mortality in elderly type 2 diabetic patients (ZODIAC-20).

AIMS: Studies on macrovascular consequences of glucose control in elderly patients (>75 years) with type 2 diabetes mellitus (T2DM) are lacking. The present study aimed to investigate the relationship between HbA(1c) and mortality in this specific population. METHODS: Between 1998 and 1999, 374 primary care patients with T2DM aged older than 75 years participated in the Zwolle Outpatient Diabetes project Integrating Available Care study, a prospective observational study. Early 2009, data on mortality were collected. Updated means for annually measured HbA(1c) values were calculated after a follow-up time of 10 years. Updated mean HbA(1c) was used as a time-dependent covariate in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular disease (CVD) mortality. Analyses were performed in strata according to diabetes duration (<5, 5-11 and ≥11 years). RESULTS: In the group with a diabetes duration <5 years, an increase of 1% in the updated mean HbA(1c) level was associated with an increase in all-cause and CVD mortality risk of 51% (95% CI 17-95%) and 72% (95% CI 19-148%), respectively. Glycaemic control was not related to mortality for patients with a diabetes duration ≥5 years. CONCLUSION: Poor glycaemic control is related to increased all-cause and CVD mortality in patients >75 years with T2DM of short duration (<5 years). DISCUSSION: Because of the observational study design, our results should be interpreted with caution. Nevertheless, they are suggestive that improving glycaemic control may be beneficial in elderly patients with T2DM, especially in those with recently diagnosed T2DM. Randomised-controlled trials are necessary to investigate whether this holds true.

Non-specific symptoms in adult patients referred to a Lyme centre.

OBJECTIVES: There is controversy whether non-specific symptoms can be related to previous Lyme borreliosis (LB). Positive serology can be considered a proxy for previous or persistent LB. We assessed non-specific symptoms and serology in patients suspected of LB referred to a Lyme centre. METHODS: Included were adult patients who visited a Lyme centre between 2008 and 2014. Before medical consultation, serum samples were taken and questionnaires on non-specific symptoms completed. The prevalence of non-specific symptoms was calculated for patients with positive and negative IgG serology. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence interval (CI) for an association between positive serology and non-specific symptoms. RESULTS: Of 1439 included patients, 31.6% (455/1439) had positive serology. The most common non-specific symptoms were severe fatigue (61.4%, 883/1439), sleep disturbances (54.8%, 789/1439) and stiffness of neck/back (52.6%, 757/1439). The prevalence of severe fatigue was 53.0% (241/455) in patients with positive serology vs. 65.2% (642/984) in patients with negative serology (OR = 0.74; 95% CI, 0.58-0.94). The prevalence of sleep disturbances was respectively 46.2% (210/455) vs. 58.8% (579/984) (OR = 0.73; 95% CI, 0.58-0.93). The prevalence of stiffness of neck/back was respectively 47.7% (217/455) vs. 54.9% (540/984) (OR = 0.85; 95% CI, 0.67-1.06). CONCLUSIONS: In patients referred to a Lyme centre, non-specific symptoms did not occur more frequently in patients with positive serology compared to patients with negative serology. Hence, a questionnaire on non-specific symptoms cannot be used for identifying patients with possible post-LB symptoms in clinical practice.

Increased cancer mortality in type 2 diabetes (ZODIAC-3).

BACKGROUND: It is unclear whether there is a relationship between type two diabetes and cancer mortality. It also is unclear whether obesity and body mass index (BMI) are associated with cancer in type 2 diabetes patients. PATIENTS AND METHODS: In 1998, 1,145 patients with type two diabetes mellitus were enrolled in the Zwolle Outpatient Diabetes project Intergrating Available Care (ZODIAC) study. In this project, general practitioners (GPs) were assisted by hospital-based diabetes specialist nurses. Vital status was assessed in September 2004. The cancer mortality rate was evaluated using standardized mortality ratio (SMR) and its association with BMI (kg/m2) and obesity (>30 kg/m2) with the Cox proportional hazard ratio. RESULTS: The median follow-up time was 5.8 years. A total of 335 patients had died, of whom 70 died from malignancy. The SMR for cancer mortality was 1.38 (95% CI 1.07-1.75). BMI and obesity were not associated with cancer death. CONCLUSION: An increased cancer mortality rate was found in type two diabetes mellitus patients but there was no significant association between BMI or obesity and cancer mortality.

Expression of vascular endothelial growth factor-C does not predict occult lymph-node metastasis in early oral squamous cell carcinoma.

Strong vascular endothelial growth factor-C (VEGF-C) expression has been correlated to occurrence of lymph-node metastases in patients with oral squamous cell carcinoma (OSCC). The incidence of occult lymph-node metastasis remains a decisive factor in the prognosis of patients with early OSCC. The aim of this study was to evaluate VEGF-C expression as a predictor of occult lymph-node metastasis in OSCC. Eighty-seven patients with primary OSCC arising in the tongue or floor of mouth, clinically T1N0M0 or T2N0M0, with (pN+) and without (pN0) occult lymph-node metastases were analyzed for VEGF-C expression by malignant cells. Occult lymph-node metastases (pN+) were detected in 22% of the 64 patients who were submitted to elective neck dissection. No statistically significant difference was found between OSCC with and without occult lymph-node metastasis in regard to VEGF-C immunoexpression by malignant cells and clinicopathologic features. Independently of VEGF-C expression, lymph-node metastasis (pN+) was the most significant prognostic factor for overall survival of patients with OSCC (p=0.030). These findings indicate that isolated VEGF-C expression by malignant cells is not of predictive value for occult lymph-node metastasis in the early stages of OSCC.

Predictive value of Borrelia burgdorferi IgG antibody levels in patients referred to a tertiary Lyme centre.

A two-step testing strategy is recommended in serological testing for Lyme borreliosis; positive and indeterminate enzyme-linked immunosorbent assay (ELISA) results are confirmed with immunoblots. Several ELISAs quantify the concentration of antibodies tested, however, no recommendation exists for an upper cut-off value at which an IgG ELISA is sufficient and the immunoblot can be omitted. The study objective was to determine at which IgG antibody level an immunoblot does not have any additional predictive value compared to ELISA results. Data of adult patients who visited a tertiary Lyme centre between 2008 and 2014 were analysed. Both an ELISA (Enzygnost Lyme link VlsE IgG) and immunoblot (recomLine blot Borrelia) were performed. Clinical data were extracted from the patient's digital medical record. Positive predictive values (PPVs) for either previous or active infection with Borrelia burgdorferi s.l. were calculated for different cut-off ELISA IgG antibody levels where the immunoblot was regarded as reference test. In total, 1454 patients were included. According to the two-step test strategy, 486 (33%), 69 (5%) and 899 (62%) patients had positive, indeterminate and negative Borrelia IgG serology, respectively. At IgG levels of 500 IU/ml and higher, all immunoblots were positive, resulting in a 100% PPV (95% CI: 97.0-100). At IgG levels of 200 IU/ml and higher, the PPV was 99.3% (95% CI: 97.4-99.8). In conclusion, at IgG levels of 200 IU/ml and higher, an ELISA was sufficient to detect antibodies to Borrelia burgdorferi s.l. At those IgG levels, a confirmatory immunoblot may be omitted in patients referred to a tertiary Lyme centre. Before these results can be implemented in routine diagnosis of Lyme borreliosis, confirmation of the results is necessary in other patient populations and using other quantitative ELISAs and immunoblots.

Health-related quality of life, rehabilitation and mortality in a nursing home population.

BACKGROUND: Health-related quality of life (HRQOL) in nursing home residents is generally low. The purpose of this study was to investigate the associations between HRQOL and two clinically relevant outcome measures, all-cause mortality and successful rehabilitation, in a nursing home population. METHODS: In an observational prospective cohort study in a nursing home population, HRQOL was assessed with the RAND-36. A total of 184 patients were included, 159 (86%) completed the RAND-36 and were included in the study. A Cox proportional hazard model was used to investigate the independent association between HRQOL, rehabilitation and mortality with adjustment for confounders. Risk prediction capabilities were assessed with Harrell's C statistics and the proportion of explained variance (R2). RESULTS: The median age (interquartile range) was 79 (75-85) years. The health dimensions vitality (HR 0.88 (95% CI 0.77-0.99)) and mental health (HR 0.86 (95% CI 0.75-0.98)) were inversely associated and role functioningphysical (HR 1.08 (95%CI 1.02-1.15)) was positively associated with mortality. The Harrell's C value and the R2 were ≤ 0.02 and ≤ 0.03 higher in the adjusted models with the dimensions role functioning- physical, mental health or vitality compared with the models without these dimensions. None of the health dimensions or summary scales were related to successful rehabilitation. CONCLUSION: HRQOL was significantly associated with mortality for three dimensions, but partly in opposite directions. Additional value of HRQOL in mortality prediction is very limited. There were no independent associations between HRQOL and successful rehabilitation. Although HRQOL is an important outcome, this study did not provide evidence for an association between HRQOL and successful rehabilitation.

Subperiosteal abscess in a child. Trueta's osteomyelitis hypothesis undermined?

Subperiosteal abscess formation is almost exclusively seen secondary to underlying hematogenous infected osteomyelitis or secondary as a result of a contagious focus. We present an unusual case of a 9-year-old girl with progressive ankle pain due to an isolated subperiosteal abscess of the distal fibula without concomitant osteomyelitis. The subperiosteal abscess was most likely caused by hematogenous spread to the periosteal region of the distal fibula located above the highly vascularized metaphysis. Remarkably, there were no signs of osteomyelitis on either MRI or during surgical inspection. She was successfully treated with debridement and antibiotic therapy. We hypothesize that subperiosteal abscess formation near the metaphysis originates in the periosteal region and not from outward extension from the sinusoidal veins in the intrametaphyseal area to the cortex and subperiosteal region.

Sex specific association between carnosinase gene CNDP1 and cardiovascular mortality in patients with type 2 diabetes (ZODIAC-22).

INTRODUCTION: Homozygosity for a 5-leucine repeat (5L-5L) in the carnosinase gene (CNDP1) has been associated with a reduced prevalence of diabetic nephropathy in cross-sectional studies in patients with type 2 diabetes, particularly in women. Prospective studies on mortality are not available. This study investigated whether 5L-5L was associated with mortality and progression of renal function loss and to what extent this effect is modified by sex. METHODS: In a prospective cohort of patients with type 2 diabetes, a Cox proportional hazard model was used to compare 5L-5L with other genotypes regarding (cardiovascular) mortality. Renal function slopes were obtained by within-individual linear regression of the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation, and were compared between 5L-5L and other genotypes. RESULTS: 871 patients were included (38% with 5L-5L). After 9.5 years of follow-up, hazards ratios (HR) for all-cause and cardiovascular mortality in 5L-5L versus other genotypes were 1.09 [95% confidence interval (CI) 0.88-1.36] and 1.12 (95% CI 0.79-1.58), respectively. There was a significant interaction between CNDP1 and sex for the association with cardiovascular mortality (p = 0.01), not for all-cause mortality (p = 0.32). Adjusted HR in 5L-5L for cardiovascular mortality was 0.69 (95% CI 0.39-1.23) in men and 1.77 (95% CI 1.12-2.81) in women. The slopes of eGFR-MDRD did not significantly differ between 5L-5L and other genotypes. CONCLUSIONS: The association between CNDP1 and cardiovascular mortality was sex-specific, with a higher risk in women with 5L-5L genotype. CNDP1 was not associated with all-cause mortality or change in eGFR.

Clinicopathologic features and human papillomavirus dna prevalence of warty and squamous cell carcinoma of the penis.

Squamous cell carcinoma (SCC) accounts for 95% of penile malignant neoplasms. A subtype of SCC, named warty carcinoma (WC), is a morphologically distinct verruciform tumor with features of human papillomavirus (HPV)-related lesions. Descriptions of the behavior and histologic features of this tumor are scarce in the literature. The aim of this report is to analyze the clinicopathologic features and HPV deoxyribonucleic acid status in 60 SCCs and 11 WCs. The mean patient age was 46.5 +/- 15.9 years for WC and 52.6 +/- 12.4 years for SCC. No significant differences in age (p = 0.154) and clinical staging (T, p = 0.649; N, p = 0.497) between the two groups of tumors were found. When compared with SCCs, WCs exhibited less lymphatic embolization (p = 0.001), nodal metastasis (p = 0.019), and corpora cavernosa and corpus spongiosum infiltration (p = 0.040). Lymph node metastases were found in 34 of 60 SCC patients (56.7%) and in two of 11 WC patients (18.2%). No patients with WC tumors died of the disease compared with 19 of 60 (5-year specific survival, 66.0%) in the SCC group (p = 0.032). HPV deoxyribonucleic acid was more likely to be associated with WC (five of 11, 45.5%) than SCC (16 of 60, 26.7%), although significance was not reached (p = 0.209). The results suggest that WC is less aggressive and confers a better prognosis than typical SCC of the penis.

Morphometric analysis of the tumor associated tissue eosinophilia in the oral squamous cell carcinoma using different staining techniques.

In a previous study, we found tumor-associated tissue eosinophilia (TATE) to be a favourable prognostic indicator for oral squamous cell carcinomas. Special techniques such as autofluorescence or immunohistochemistry are reported to be sometimes necessary to detect the presence of intact and degranulating eosinophils within the tumors. The aim of this study was to compare the number of eosinophils identified routinely with hematoxylin and eosin stain and by immunohistochemistry in oral squamous cell carcinomas with TATE. Thirty specimens of oral squamous cell carcinoma of the tongue, floor of the mouth, retromolar area and inferior gingiva with TNM stages II and III were used for histopathological analysis. Three-micrometer sections were stained with hematoxylin and eosin and immunohistochemically with monoclonal anti-human granulocyte-associated antigen using a standard streptavidin-biotin-peroxidase complex technique. The number of eosinophils/mm2 in the invasive front of the tumors was automatically quantified in a x400 field using an image computer analyser. Univariate statistical analysis was carried out using Student's t test. The computer-assisted morphometric results showed that there was no statistically significant difference (p>0.05) in the number of eosinophils/mm2 identified by hematoxylin and eosin or immunostaining technique in oral squamous cell carcinomas with TATE. This result suggests that hematoxilyn and eosin routine stain is a useful technique for measuring eosinophils in squamous cell carcinoma with eosinophilic tumor infiltration.

Opportunistic actinomycosis in osteoradionecrosis of the jaws in patients affected by head and neck cancer: incidence and clinical significance.

Actinomycosis is occasionally an opportunistic infection occurrence in patients with osteoradionecrosis (ORN). A retrospective study (1992-97) of 50 patients with ORN of the jaws was done to evaluate the incidence and its clinical significance in the management of ORN. Actinomycosis was diagnosed in 12% of ORN cases. In 36 of the 50 patients including five cases of actinomycosis, the ORN was considered to be resolved after treatment. The median treatment duration of ORN was significantly longer (P<0.007) in patients with actinomycosis (29.7 months) than those without the disease (13.4 months). In conclusion, bone biopsy should be considered in cases of ORN with unsatisfactory response to its specific therapies, aiming to identify possible opportunistic actinomycosis infection.

Coronary-pulmonary fistula: long-term follow-up in operated and non-operated patients.

Eleven cases with 13, incidentally found coronary-pulmonary fistulous communications were discovered out of about 11,000 diagnostic coronary angiograms performed in different patients, over the period 1968 to 1989. These patients were followed-up for an average period of 4.4 years (range 2-11 years). The majority had a fistulous malformation originating from the proximal part of the left anterior descending artery and terminating in the pulmonary trunk. In three subjects, the right coronary artery participated in formation of the shunt. The fistulas consisted either of a convoluted mass of serpentive vessels, sometimes with aneurysmal formation, or of a solitary single vessel. Angina pectoris, atypical chest pain and fatigue were the most common symptoms. All patients were treated conservatively except one, who underwent ligation of the fistula and coronary arterial bypass grafting. Two subjects are still free of symptoms. No death occurred. None of the patients developed subacute bacterial endocarditis, acute myocardial infarction or left ventricular failure during the period of follow-up of more than four years. Three individuals, prior to the follow-up period, had suffered myocardial infarction contralateral to the shunt. They had no recurrence.