Consequences For Clinical Management Research Articles

The Effect of Iron Deficiency Anemia on Hemoglobin Glycation in Diabetics and Non-diabetics.

Background Iron deficiency anemia (IDA) is the most prevalent form of nutritional anemia worldwide, affecting a substantial portion of the population. It has significant negative effects on health and the economy, especially in poorer nations, and is more prevalent than anemia alone. Although hemoglobin A1c (HbA1c) is frequently used to track long-term glycemic management, several variables, including iron deficiency, might affect its values.For proper diabetic care, it is essential to comprehend this link. The purpose of this study is to evaluate the impact of IDA on HbA1c levels in individuals with and without diabetes. Materials and methods A hospital-based cross-sectional study was conducted at Shri B. M. Patil Medical College, BLDE (Deemed to be University). Group 1 consists of diabetic patients with IDA, Group 2 consists of diabetic patients without IDA, and Group 3 consists of non-diabetics with IDA. A total of 108 patients were involved in the study. A complete hemogram, anemia profile, and HbA1c values were also a part of the data-gathering process. IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York) was used for the statistical analysis, with a significance level of p < 0.05. Results The study found no significant changes in the mean age, gender distribution,hypertension prevalence, weight, height, pulse rate, or blood pressure across the groups. Group 2 exhibited considerably higher hemoglobin levels than Groups 1 and3. Group 1 showed substantially higher mean blood sugar and HbA1c levelsthan Group 3 (p < 0.05). Diabetic individuals had higher HbA1c levels than non-diabetic individuals, with the greatest levels found in diabetic patients with IDA. Conclusion This study found that IDA had a significant influence on HbA1c levels in diabetic patients, indicating that iron deficiency should be addressed when interpreting HbA1c levels in these individuals. These findings underscore the need for more study to better understand the processes behind this connection and the consequences for clinical management.

ECG-gated MR angiography at 3T for follow-up after surgery involving the ascending aorta.

We aimed to evaluate electrocardiogram (ECG)-gated MR angiography (MRA) in the follow-up after surgery involving the ascending aorta regarding technical feasibility, image quality, spectrum of findings, and their implications for clinical management. We retrospectively analyzed a cohort of 19 patients (median age 59 years, range 38-79 years), who underwent MRA for follow-up imaging after surgery involving the ascending aorta. Our magnetic resonance imaging protocol consisted of a time-resolved, non-ECG-gated MRA and an ECG-gated MRA performed at 3T. Median examination duration was 25 minutes (range 11-41 minutes). All examinations were assessed by 2 readers in consensus for image quality on a 5-point scale ranging from 1 (non-diagnostic) to 5 (excellent). MRA examinations and patient charts were analyzed for diagnostic findings and their consequences for further management. Subjective image quality was rated as "sufficient" (score 3.1 ± 1.1) for the aortic root and as "good" to "excellent" for the ascending aorta (score 4.5 ± 0.7), aortic arch (4.5 ± 0.7), supra-aortic branches (4.5 ± 0.6) and descending aorta (4.6 ± 0.7). Abnormal findings were seen in 6 patients (32%) including progressive diameter of remaining aneurysm or dissection (3 patients, 16%) and suture aneurysms (3 patients, 16%). In all 6 of these patients, abnormal findings at MRA had consequences for clinical management. ECG-gated MR angiography at 3T yields good image quality for post-operative surveillance after aortic surgery involving the ascending aorta. This technique may serve as an alternative to computed tomography particularly in younger patients with repeated follow-up.

Case report: appendicitis induced Staphylococcus aureus and Klebsiella pneumoniae bacteremia in a young healthy male

BackgroundAppendicitis is one of the most frequently encountered conditions at the emergency department. Distinction is made between complicated and uncomplicated appendicitis. Complicated appendicitis may cause serious intra-abdominal infection, bacteremia, or sepsis. Emergency health providers should be highly alert to any early signs indicating such complications.Case presentationWe present the case of a healthy young male with a gangrenous appendicitis, who received antibiotics and underwent appendectomy. Blood cultures showed unequivocal Staphylococcus aureus and concomitant Klebsiella pneumoniae bacteremia requiring prolonged antibiotic treatment and further diagnostic evaluation.ConclusionsAlthough rare, appendicitis can cause Staphylococcus aureus and Klebsiella pneumoniae bacteremia with extensive implications for workup and antibiotic management. Our case stresses the importance of obtaining cultures in patients with suspicion of bacteremia given its consequences for clinical management.

Diversity and characterization of HIV-1 subtypes in the United States, 2008–2016

PurposeThis article describes subtype diversity among diagnosed HIV-1 infections in the United States during 2008–2016 by demographic or risk group and over time. MethodsHIV-1 polymerase sequences reported to the National HIV Surveillance System for persons in 17 U.S. states with HIV infection diagnosed during 2008–2016 were subtyped using COMET, an automated subtyping tool, and National HIV Surveillance System demographic data were analyzed. ResultsSubtype B was identified in 93.6% of 121,793 reported sequences. The most common non-B subtypes and circulating recombinant forms (CRFs) were C, CRF02_AG, A, CRF01_AE, and G. Elevated percentages of non-B subtypes or CRFs were found in persons who were female, aged less than 13 years at diagnosis, Asian, or had transmission attributable to heterosexual contact (females only) or perinatal exposure. Foreign-born persons had a higher percentage of non-B subtypes. The prevalence of non-B subtypes and CRFs increased from 5.0% in 2008 to 8.5% in 2016; among specific subtypes and CRFs, subtype G and CRF01_AE increased. ConclusionsSubtype B remains the predominant strain in the United States. Non-B subtypes and CRFs were not widespread, but diversity and numbers increased from 2008 through 2016, which could have consequences for clinical management, diagnostic testing, and vaccine development.

Invasive cervical tumors with high and low HPV titer represent molecular subgroups with different disease etiology.

Invasive cervical cancer (ICC) with very low titer of high-risk human papillomavirus (HPV) has worse clinical outcome than cases with high titer, indicating a difference in molecular etiology. Fresh-frozen ICC tumors (n = 49) were classified into high- and low-HPV-titer cases using real-time PCR-based HPV genotyping. The mutation spectra were studied using the AmpliSeq Comprehensive Cancer Panel and the expression profiles using total RNA sequencing, and the results were validated using the AmpliSeq Transcriptome assay. HPV DNA genotyping and RNA sequencing showed that 16.6% of ICC tumors contained very low levels of HPV DNA and HPV transcripts. Tumors with low HPV levels had more mutations with a high allele frequency and fewer mutations with low allele frequency relative to tumors with high HPV titer. A number of genes showed significant expression differences between HPV titer groups, including genes with somatic mutations. Gene ontology and pathway analyses implicated the enrichment of genes involved in DNA replication, cell cycle control and extracellular matrix in tumors with low HPV titer. The results indicate that in low titer tumors, HPVs act as trigger of cancer development whereas somatic mutations are clonally selected and become drivers of the tumor development process. In contrast, in tumors with high HPV titer the expression of HPV oncoproteins plays a major role in tumor development and the many low frequency somatic mutations represent passengers. This putative subdivision of invasive cervical tumors may explain the higher radiosensitivity of ICC tumors with high HPV titer and thereby have consequences for clinical management.

Childhood Secondhand Tobacco Smoke Exposure and Ovarian Reserve Among Females Seeking Fertility Care, and Interaction with N- Acetyltransferase 2(NAT2) Genotype

This article describes subtype diversity among diagnosed HIV-1 infections in the United States during 2008–2016 by demographic or risk group and over time.HIV-1 polymerase sequences reported to the National HIV Surveillance System for persons in 17 U.S. states with HIV infection diagnosed during 2008–2016 were subtyped using COMET, an automated subtyping tool, and National HIV Surveillance System demographic data were analyzed.Subtype B was identified in 93.6% of 121,793 reported sequences. The most common non-B subtypes and circulating recombinant forms (CRFs) were C, CRF02_AG, A, CRF01_AE, and G. Elevated percentages of non-B subtypes or CRFs were found in persons who were female, aged less than 13 years at diagnosis, Asian, or had transmission attributable to heterosexual contact (females only) or perinatal exposure. Foreign-born persons had a higher percentage of non-B subtypes. The prevalence of non-B subtypes and CRFs increased from 5.0% in 2008 to 8.5% in 2016; among specific subtypes and CRFs, subtype G and CRF01_AE increased.Subtype B remains the predominant strain in the United States. Non-B subtypes and CRFs were not widespread, but diversity and numbers increased from 2008 through 2016, which could have consequences for clinical management, diagnostic testing, and vaccine development.

Functional considerations in ALPPS – consequences for clinical management

BackgroundSince perioperative morbidity and mortality in ALPPS are extraordinarily high, a deeper understanding of actual liver function during the procedure is essential to make the approach safer. MethodsData from 17 patients who underwent ALLPS were analyzed regarding their course of liver function capacity assessed with the LiMAx test and compared to an equal-sized matched cohort of patients that underwent PVE. ResultsA comparison of LiMAx prior to and following ALPPS Step I (330 [258–385] vs. 197 [144–224] μg/kg/h, p = 0.003) and prior to and following PVE (386 [330–519] vs. 378 [336–455] μg/kg/h, p = 0.534) demonstrated a significant drop in function after ALLPS. A volume/function analysis predicting FLR function regarding step II revealed an excellent correlation of predicted versus assessed postoperative liver function with a mean relative difference of 9 (−6 to 18)% and an ICC of 0.905 (123 [74–138] vs. 107 [77–175] μg/kg/h, p = 0.310). ConclusionsWe provide evidence that liver function capacity is significantly impaired due to ALPPS step I. This is particularly notable when compared to PVE. Our data also shows that the portal ligated liver lobe still continues to contribute significantly to overall liver function. Therefore, FLR function after step II is still predictable by volume/function analysis.

Intra-patient variability in tacrolimus exposure: causes, consequences for clinical management.

Tacrolimus (Tac) is widely used for the prevention of rejection after solid organ transplantation. Finding the optimal balance between effective Tac concentrations and toxicity is a challenge and requires therapeutic drug monitoring. In addition to the well-known inter-patient variability, the clinical use of Tac is also complicated by considerable intra-patient variability (IPV) in Tac exposure. Tac IPV is defined as the amount of fluctuation of whole-blood concentrations over a certain period of time during which the Tac dose remains unchanged. A high IPV in Tac exposure has recently been recognized as a strong risk factor for acute rejection and poor long-term kidney transplantation outcome. In addition to non-adherence, several other factors determine the magnitude of the IPV in Tac exposure. Quantification of IPV is easy and can be easily incorporated into everyday clinical practice as a tool for optimizing transplantation outcomes.

Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea

Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

Comparative biomechanical analysis of gait in patients with central cord and Brown-Séquard syndrome

Purpose: This is a pilot study with the aim to highlight the use of kinematic and kinetic analyses as an adjunct to the assessment of individual patients with central cord syndrome (CCS) and hemisection or Brown-Séquard syndrome (BSS) and to discuss their possible consequences for clinical management. Methods: The sample studied consisted of 17 patients with CCS, 13 with BSS and 20 control subjects (control group (CG)). Data were obtained using a three-dimensional motion analysis system and two force plates. Gait differences were compared between CCS, BSS walking at a self-selected speed and CG at both a self-selected and a similar speed to that of the patient groups. Results: The most relevant findings involved the knee and ankle, especially in the sagittal plane. In patients with CCS, knee flexion at initial contact was increased with respect to those in the BSS group (p < 0.01). The ankle in the BSS group made initial contact with a small degree of plantar flexion. Conclusion: The use of gait biomechanical analysis to detect underlying impairments can help the physician to set a specific rehabilitation program in each CCS and BSS walking patient. In this group of patients, rehabilitation treatment should aim to improve gait control and optimise ankle positioning at initial contact.Implications for RehabilitationIn this study, gait differences between patients with CSS and BSS were evaluated with biomechanical equipment.The most remarkable differences were found in the knee and ankle sagittal plane due to ankle position at initial contact.In this group of patients, rehabilitation treatment should aim to improve gait control and to get a better ankle positioning at initial contact.

Letter to the Editor - The BRAF V600E Mutation is Not Present in All Cells of the Primary Melanoma and May Not Be Detected in All Metastatic Sites

The invention of targeted therapy for advanced stage melanoma has made it necessary to perform a mutation analysis of each melanoma case in order to detect the BRAF V600E mutation required for the prescription of selective BRAF inhibitors. In this new clinical context it is important to realize that the tumour seeds may come from different tumour clones and thus not all carry the mutation. We present an illustrative case that shows this phenomenon and discuss the consequences for clinical management in case of possible false negative mutation testing.

Familial primary pigmented nodular adrenocortical disease without Carney complex (CNC): A case report and review of literature

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of familial Cushing's syndrome. It is characterized by bilateral adrenocortical hyperplasia with small to normal-sized adrenal glands containing multiple small adrenal cortical pigmented nodules [1,2]. PPNAD may occur in an isolated form or as familial PPNAD. Familial cases of PPNAD are usually associated with Carney complex in which Cushing’s syndrome is the most common endocrine manifestation [3]. Familial cases of PPNAD without associated Carney complex are very rare. Only a few cases of familial isolated PPNAD have been reported in the literature, mostly in females [4]. Isolated familial PPNAD has got a better prognosis than familial PPNAD associated with Carney Complex. This observation has important consequences for clinical management, follow-up and genetic counselling of such patients. Familial cases of PPNAD are rare and mostly present in females with associated Carney complex. We herein report a case of familial Cushing’s syndrome in male siblings due to PPNAD without associated Carney complex.

Normal and abnormal development of pulmonary veins: State of the art and correlation with clinical entities

Interest for the pulmonary veins has increased in the past decade after the potential arrhythmogenicity of the myocardial sleeve surrounding these structures has been recognized. Furthermore, there are several clinical entities, such as anomalous connection pattern and pulmonary vein stenosis, that are related to abnormal pulmonary vein development. In this review, we will describe current literature and aim to elucidate and reorganize current opinions on normal and abnormal pulmonary vein development in relation to clinical (management of) diseases. Several unresolved questions will be addressed, as well as current conceptual controversies. First, a general overview of development of structures at the venous pole of the heart, including normal development of the pulmonary vein from a primitive Anlage, will be provided. Recent insights indicate an important contributory role of the mesoderm behind the heart, the so-called second heart field, to this area. Subsequently, the formation of a myocardial and smooth muscle vascular wall of the pulmonary veins and the left atrium is described, as well as current insights in the mechanisms involved in the differentiation of these different cell types in this area. Next, developmental concepts of normal pulmonary venous drainage patterns are reviewed, and an overview is provided of clinical entities related to abnormal development at several anatomical levels. Lastly, attention is paid to arrhythmogenesis in relation to pulmonary vein development, as well the consequences for clinical management.

Natural history of testicular regression syndrome and consequences for clinical management

Aims Testicular regression syndrome (TRS or ‘vanishing testis’) is a condition in which a testis is thought to have once existed but has atrophied and disappeared during early development. The natural history of TRS is in completely understood, due to the absence of any prospectively studied cohort of patients. This study aimed to quantify the cardinal features of the disease and correlate these with age. Materials and methods A total of 117 cases of TRS were submitted for histopathological examination. Patient age ranged from birth to 12 years, with a median age of 2 years. The proportion of each histological feature present was analysed according to age, using the χ 2 test. Birth Results The 117 cases accounted for 21% of the testicular/paratesticular specimens examined. Only 12 cases (10%) were found to contain testicular tissue, with no readily identifiable germ cells and in particular no atypical germ cells identified. Features such as haemosiderin-laden macrophages, calcification, the presence of a nodule, vas or epididymis were less prevalent amongst specimens from older boys. Conclusions This is the largest series studied to date. With only 10% of the removed specimens containing identifiable testicular tissue with no germ cells seen, a negligible risk of future germ-cell cancer on the affected side is implied. If the laparoscopic findings suggest a diagnosis of vanishing testis, we contend that a groin exploration may be no longer indicated.

Making sense of aches and pains

The uncertainty about the status of upper limb disorders (ULDs), particularly the non-specific conditions, is believed to have consequences for clinical management and patient care. This paper presents evidence about how sufferers with ULDs respond to their pain, how their pain is managed, when and who they go to for formal help and how sufferers evaluate the care they receive. The data analysis is derived from face-to-face, informal interviews with sufferers with a broad spectrum of upper limb disorders (n = 47). These informants were selected according to strict criteria from a 'screening' postal survey of the working population (25-64 years) in south-west England (n = 2781). Ideas about causation were crucial to understanding patterns of illness action and help seeking behaviour. The common strategy was to wait and see what happens as the pain was believed to be a natural part of the ageing process. Explanations invoking psychosocial and work related causes were less common and tended to be used when biomechanical explanations were no longer appropriate. Self-management was the preferred strategy but orthodox practitioners were usually the first choice for formal care. Complementary and alternative medicines (CAM) were popular but were used to complement orthodox care. Practitioners were evaluated mainly in terms of their ability to alleviate pain. There is a need for orthodox and non-orthodox care to be closely integrated in primary care and GPs should not depend on orthodox medications alone when caring for patients with upper limb pain.

Improved Detection of Urothelial Carcinoma In Situ With Hexaminolevulinate Fluorescence Cystoscopy

In this European multicenter study we compared hexaminolevulinate (HAL) fluorescence cystoscopy and standard white light cystoscopy for the detection of carcinoma in situ (CIS) in patients suspected of having high risk bladder cancer. This study was a prospective controlled, within-patient comparison of standard and HAL fluorescence cystoscopy. Eligible patients received an intravesical instillation of 50 ml HAL 8 mM solution. Cystoscopy was performed using a D light system, which provided white and blue light at 375 to 440 nm. The bladder wall was inspected and mapped, first under white light, followed by blue light. All tumors and suspicious areas identified under white light and by red fluorescence were resected or biopsied. Histological findings were assessed by an independent central pathologist blinded to the identity of the biopsies. Of 211 evaluable patients 83 (39%) had CIS, of whom 18 (22%) were detected by HAL cystoscopy only, 62 (75%) were detected by standard and HAL cystoscopy, 2 (2%) were detected by standard cystoscopy only and 1 (1%) was detected by nonguided biopsy. Therefore, HAL cystoscopy identified 28% more patients with CIS than standard cystoscopy. The side effects of HAL instillation were negligible and no unexpected events were reported. HAL fluorescence cystoscopy improves the detection of bladder CIS significantly, which has consequences for clinical management and may improve the patient prognosis. The procedure is easily implemented as an adjunct to standard cystoscopy and it adds no significant risk of complications.

Fetal behaviour in uncomplicated pregnancies after 41 weeks of gestation

The development of fetal behaviour and of fetal behavioural states (FBS) has been well defined in preterm and term fetuses. However, FBS have not yet been studied after term, although this is a potentially very dangerous period and clinical management is controversial. We investigated fetal behaviour in normal pregnancies after 41 weeks of gestation (287 days, menstrual age, GA) as compared to control term fetuses. Furthermore, we wanted to see if the findings might have consequences for clinical management. Twelve healthy women with GA between 289 and 298 days participated. All pregnancies were reliably dated and at the time of the study, there was a normal amount of fluid. Twelve healthy women with GA 273–287 days served as controls. All subjects underwent a behavioural study using cardiotocography to record the heart rate (CTG), and two ultrasound scanners to observe body and eye movements, as described previously. All fetuses in both groups clearly exhibited FBS 1F-4F which fitted the definitions of Nijhuis et al. [5]. The median percentage of FBS 3F and 4F (‘awake states’) increased significantly from 6% in the term group to 21.5% in the fetuses after 41 weeks ( P = 0.014). FBS 1F (‘quiet sleep’) and 2F (‘active sleep’) decreased from 92 to 78% ( P = 0.014), mainly at the expense of FBS 2F which decreased from 78 to 58% ( P = 0.002). This indicates increasing wakefulness in utero. The fetal heart rate patterns (FHRP) associated with FBS 3F and 4F were impressive. For example, in FBS 4F, the FHRP showed large amplitude, prolonged accelerations which fused into a sustained tachycardia with only short periods of return to the baseline, resembling tachycardia with decelerations. We conclude that in normal pregnancies after 41 weeks, the development of the fetal central nervous system continues, resulting in an increasing percentage of ‘fetal wakefulness’. The CTG-patterns that result from these behaviours can easily mimic fetal distress and one should be aware of this phenomenon. Whether behavioural studies can be used to distinguish ‘normal’ from ‘abnormal’ fetuses after term awaits further study.

Invasive techniques of prenatal diagnosis

The last 10–15 years have seen the development of both obstetrical and laboratory techniques which have made the field of prenatal diagnosis almost a speciality in itself. A number of invasive procedures are now available which allow access to the fetus and its environment, and enable the diagnosis of congential disorders, either by analysis of the genotype or by study of phenotypical changes. This has been the basis for a new understanding of fetal pathophysiology, with consequences for clinical management which are still being defined. New techniques have been developed and older ones are being reappraised. The aim of this review is to give a brief summary of this continuous, often unsettling, process.