Obesity and abdominal hernia in ambulatory patients, 2018-2023.

PURPOSE: To determine the relationship between abdominal hernia and obesity. Although obesity is frequently cited as a risk factor for abdominal hernia, few studies have confirmed this association (Menzo et al. Surg Obes Relat Dis 14:1221-1232. 10.1016/j.soard.2018.07.005, 2018). METHODS: A cross-sectional study of primary care ambulatory patients aged older than 16 years treated at UCLA Health from 01/01/2018 to 06/06/2023. Abdominal hernia was identified by clinic encounter ICD-10 codes (K40-K46). RESULTS: There were 41,703 hernias identified among 1,362,440 patients (306.1 per10,000) with a mean age of 62.5 ± 16.1 years, and 57.6% were men. Nearly half (44.7%) of all abdominal hernias were diaphragmatic. There was an approximately equal distribution of the ventral (28.7%) and inguinal (24.3%) hernia. Each hernia type had a different relationship with obesity: The odds of having a ventral hernia increased with BMI in both sexes: BMI 25-29.9 kg/m2 odds ratio (OR) = 1.65, (CI 1.56-1.74); BMI 30-39.9 kg/m2 OR = 2.42 (CI 2.29-2.56), BMI 40-49.9 kg/m2 OR = 2.28 (CI 2.05-2.54) and BMI > = 50 kg/m2 OR = 2.54 (CI 2.03-3.17) all relative to normal BMI. In contrast, the odds of having an inguinal hernia decreased with obesity relative to normal weight [obesity (BMI 30-39.9 kg/m2): OR = 0.60 (CI 0.56-0.65)], morbid obesity (BMI 40-49.9 kg/m2): OR = 0.29 (CI 0.23-0.37). The OR for diaphragmatic hernia peaks with obesity in women and overweight status in men but was found to decrease with morbid obesity [OR = 1.18 (CI 1.07-1.30)]. There was no significant difference between men and women in the prevalence of femoral hernia (men: 0.7/per10,000, women: 0.9/per10,000, p = 0.19). CONCLUSIONS: The relationship between hernia and obesity is complex with some hernias decreasing in prevalence as obesity increases. Further research is needed to better understand this paradoxical relationship.

Climbing and Clinging of Urban Lizards are Differentially Affected by Morphology, Temperature, and Substrate.

Urbanization alters the environment along many dimensions, including changes to structural habitat and thermal regimes. These can present challenges, but may also provide suitable habitat for certain species. Importantly, the functional implications of these habitat shifts can be assessed through the morphology-performance-fitness paradigm, though these relationships are complicated by interactions among habitat choice, other abiotic factors, and morphology across scales (i.e., micromorphology and gross anatomy). The common wall lizard (Podarcis muralis) is one example of a cosmopolitan and successful urban colonizer. Quantifying both shifts in morphology over time and morphology-performance relationships under various ecological contexts can provide insight into the success of species in a novel environment. To examine how morphological variation influences performance, we measured seven gross morphological characteristics and utilized scanning electron microscopy to obtain high-resolution images of a claw from individuals living in established populations in Cincinnati, Ohio, USA. We used a geometric morphometric approach to describe variation in claw shape and then compared the claws of contemporary lizards to those of museum specimens collected approximately 40 years ago, finding that claw morphology has not shifted over this time. We then performed laboratory experiments to measure the clinging and climbing performance of lizards on materials that mimic ecologically relevant substrates. Each individual was tested for climbing performance on two substrates (cork and turf) and clinging performance on three substrates (cork, turf, and sandpaper) and at two temperatures (24ºC and 34ºC). Clinging performance was temperature insensitive, but determined by substrate-specific interactions between body dimensions and claw morphology. Conversely, the main determinant of climbing performance was temperature, though lizards with more elongate claws, as described by the primary axis of variation in claw morphology, climbed faster. Additionally, we found strong evidence for within-individual trade-offs between performance measures such that individuals who are better at clinging are worse at climbing and vice versa. These results elucidate the complex interactions shaping organismal performance in different contexts and may provide insight into how certain species are able to colonize novel urban environments.

A Health Services Research Agenda for Bariatric Surgery Within the Veterans Health Administration.

In 2016, the Veterans Health Administration (VHA) held a Weight Management State of the Art conference to identify evidence gaps and develop a research agenda for population-based weight management for veterans. Included were behavioral, pharmacologic, and bariatric surgery workgroups. This article summarizes the bariatric surgery workgroup (BSWG) findings and recommendations for future research. The BSWG agreed that there is evidence from randomized trials and large observational studies suggesting that bariatric surgery is superior to medical therapy for short- and intermediate-term remission of type 2 diabetes, long-term weight loss, and long-term survival. Priority evidence gaps include long-term comorbidity remission, mental health, substance abuse, and health care costs. Evidence of the role of endoscopic weight loss options is also lacking. The BSWG also noted the limited evidence regarding optimal timing for bariatric surgery referral, barriers to bariatric surgery itself, and management of high-risk bariatric surgery patients. Clinical trials of pre- and post-surgery interventions may help to optimize patient outcomes. A registry of overweight and obese veterans and a workforce assessment to determine the VHA's capacity to increase bariatric surgery access were recommended. These will help inform policy modifications and focus the research agenda to improve the ability of the VHA to deliver population-based weight management.

Joint bleeding in factor VIII deficient mice causes an acute loss of trabecular bone and calcification of joint soft tissues which is prevented with aggressive factor replacement.

While chronic degenerative arthropathy is the main morbidity of haemophilia, a very high prevalence of low bone density is also seen in men and boys with haemophilia. This study investigates bone degradation in the knee joint of haemophilic mice resulting from haemarthrosis and the efficacy of aggressive treatment with factor VIII in the period surrounding injury to prevent bone pathology. Skeletally mature factor VIII knock-out mice were subjected to knee joint haemorrhage induced by puncture of the left knee joint capsule. Mice received either intravenous factor VIII treatment or placebo immediately prior to injury and at hours 4, 24, 48, 72 and 96 after haemorrhage. Mice were killed 2-weeks after injury and the joint morphology and loss of bone in the proximal tibia was assessed using microCT imaging. Quantitative microCT imaging of the knee joint found acute bone loss at the proximal tibia following injury including loss of trabecular bone volumetric density and bone mineral density, as well as trabecular connectivity density, number and thickness. Unexpectedly, joint injury also resulted in calcification of the joint soft tissues including the tendons, ligaments, menisci and cartilage. Treatment with factor VIII prevented this bone and soft tissue degeneration. Knee joint haemorrhage resulted in acute changes in adjacent bone including loss of bone density and mineralization of joint soft tissues. The rapid calcification and loss of bone has implications for the initiation and progression of osteoarthritic degradation following joint bleeding.

Reconciliation of international administrative coding systems for comparison of colorectal surgery outcome.

AIM: Significant variation in colorectal surgery outcomes exists between different countries. Better understanding of the sources of variable outcomes using administrative data requires alignment of differing clinical coding systems. We aimed to map similar diagnoses and procedures across administrative coding systems used in different countries. METHOD: Administrative data were collected in a central database as part of the Global Comparators (GC) Project. In order to unify these data, a systematic translation of diagnostic and procedural codes was undertaken. Codes for colorectal diagnoses, resections, operative complications and reoperative interventions were mapped across the respective national healthcare administrative coding systems. Discharge data from January 2006 to June 2011 for patients who had undergone colorectal surgical resections were analysed to generate risk-adjusted models for mortality, length of stay, readmissions and reoperations. RESULTS: In all, 52 544 case records were collated from 31 institutions in five countries. Mapping of all the coding systems was achieved so that diagnosis and procedures from the participant countries could be compared. Using the aligned coding systems to develop risk-adjusted models, the 30-day mortality rate for colorectal surgery was 3.95% (95% CI 0.86-7.54), the 30-day readmission rate was 11.05% (5.67-17.61), the 28-day reoperation rate was 6.13% (3.68-9.66) and the mean length of stay was 14 (7.65-46.76) days. CONCLUSION: The linkage of international hospital administrative data that we developed enabled comparison of documented surgical outcomes between countries. This methodology may facilitate international benchmarking.

The Kushida Index as a screening tool for obstructive sleep apnoea-hypopnoea syndrome.

OBJECTIVES: To test the validity of the Kushida Index for screening for sleep apnoea in a West of Scotland adult population. METHODS: Specific intra-oral measurements and respiratory polysomnography were carried out on 71 patients in this prospective study. The intra-oral measurements were applied to the Kushida formula to obtain a value for the Kushida Index. This value was compared to the diagnosis obtained using polysomnography in the conventional manner. RESULTS: The sensitivity of the Kushida Index in this present study was 68% (95% CI 50-81) and the specificity was 71% (95% CI 52-84). The positive predictive value was 71% and the negative predictive value was 67%. The Mallampati score, Epworth sleepiness score and enlargement of the tongue, soft palate or tonsils were not statistically significantly related to a diagnosis of sleep apnoea (p >0.05). CONCLUSION: With the limited sensitivity and specificity of the Kushida Index demonstrated in this study, this test cannot be recommended as a screening tool for sleep apnoea in a West of Scotland population.

The attitudes of general dental practitioners and medical specialists to the provision of intra-oral appliances for the management of snoring and sleep apnoea.

AIM: To determine the attitudes and awareness of dental and medical practitioners in Scotland to the provision of oral appliances for the management of snoring and sleep apnoea. SETTING: The questionnaire was completed by general dental practitioners randomly selected from across Scotland and by doctors specialising in sleep medicine within Scotland. METHOD: A questionnaire was devised and sent to 17 specialists in sleep medicine and 210 general dental practitioners, community dental service practitioners and hospital-based dental practitioners. A reply-paid envelope was included with each questionnaire. RESULTS: There were 14 replies (82%) from specialists and 105 (50%) from dentists. All the specialists felt that dentists had a role in the management of these patients. Of the replies from dentists, 60 (57%) stated that they provided appliances but their screening for sleep apnoea and discussion of the side-effects of appliances varied widely. Seventy-eight dentists (74%) expressed an interest in attending a course on the management of sleep apnoea and snoring. CONCLUSIONS: The current practice of specialists and dentists in the management of obstructive sleep apnoea and socially disruptive snoring with oral appliances in Scotland is varied. Many dentists expressed a wish for further training in this area.

Role of symptoms and lung function in determining asthma control in smokers with asthma.

BACKGROUND: Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known. AIM OF THE STUDY: The aim of this study was to compare asthma control in smokers vs never-smokers with asthma, using the validated Juniper asthma control questionnaire (ACQ), and assess if any difference was because of a particular symptom or the forced expiratory volume in one second (FEV(1)) value. METHODS: This was a cross-sectional study of 134 asthmatics (74 never-smokers and 60 smokers) with >or=15% reversibility in FEV(1) after salbutamol. All subjects completed the ACQ, recording FEV(1) and asthma symptoms (night awakening, morning symptoms, dyspnoea, wheeze, activity limitation and use of reliever inhaler). RESULTS: Compared with the never-smokers, smokers with asthma had significantly worse median (IQR) total asthma control score [1.6 (1.1-2.3) vs 2.8 (1.7-3.4); (P < 0.0001)] and in each of the six individual symptom question scores (P < 0.001), but no difference in FEV(1) levels (P = 0.908). CONCLUSION: Asthma control is significantly worse in asthmatics who smoke compared with never-smokers, with all symptoms related to asthma control uniformly worse in smokers, independent of FEV(1).

Systemic sensitivity to corticosteroids in smokers with asthma.

Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.

Serum and sputum neurotrophin levels in chronic persistent cough.

BACKGROUND: Neurotrophins (NTs) are a family of growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin3 (NT-3) that are involved in inflammation. Serum and induced sputum NT levels are increased in asthma and in cough because of idiopathic pulmonary fibrosis, respectively. Neurogenic inflammation is implicated in the pathogenesis of chronic cough in individuals with normal chest radiography, but the role of NTs in this condition is unknown. OBJECTIVE: To assess if NT levels are elevated in the serum and airways in subjects with chronic persistent cough. METHODS: Eighty-one subjects with chronic cough persistent for over 1 year; with normal chest radiography and spirometry were included. Thirty healthy subjects were controls. Serum NGF, BDNF and NT-3 were measured by enzyme immunoassay. In a subset, NGF was measured in induced sputum. Sputum cell counts and allergen-specific serum IgE were measured and all patients received specific sequential treatment trials to achieve a final diagnosis for the cough. RESULTS: There was no significant difference either in the levels of serum or sputum NTs in chronic cough subjects compared with controls or between the most common causes of cough: post-nasal drip syndrome, gastro-oesophageal reflux disease, asthma and bronchiectasis. The median (inter-quartile range) for sputum NGF (pg/mL) was 516 (296-772) in healthy controls and 580 (312-880) in subjects with chronic cough (P=0.284). There was no correlation between NT levels and sputum cell counts. Sputum NGF levels correlated with duration of cough (r=0.34, P=0.002). CONCLUSION: NTs are not elevated in induced sputum or serum of subjects with chronic persistent cough. This implies that NTs do not have a central role in perpetuating airway inflammation in chronic persistent cough.

Asthma and cigarette smoking.

In most developed countries approximately 25% of adults with asthma are current cigarette smokers. Asthma and active cigarette smoking interact to cause more severe symptoms, accelerated decline in lung function, and impaired short-term therapeutic response to corticosteroids. Cigarette smoking may modify inflammation that is associated with asthma, although there is limited published data on airway pathology in smokers with asthma. To date, the evidence points towards a combination of both heightened and suppressed inflammatory responses in smokers compared with nonsmokers with asthma. The mechanisms of corticosteroid resistance in asthmatic smokers are unexplained, but could be as a result of alterations in airway inflammatory cell phenotypes (e.g. increased neutrophils or reduced eosinophils), changes in the glucocorticoid receptor-alpha to -beta ratio (e.g. overexpression of glucocorticoid receptor beta), and increased activation of pro-inflammatory transcription factors (e.g. nuclear factor-kappaB) or reduced histone deacetylase activity. In conclusion, every effort should be made to encourage asthmatics who smoke to stop, although the effects of smoking cessation upon reversing the adverse effects of tobacco smoke on asthma control, therapeutic response to corticosteroids and airway pathology have yet to be fully elucidated. Alternative or additional therapies to inhaled corticosteroids are needed for asthmatic patients who are unable to quit smoking.

Biexponential model for predicting weight loss after gastric surgery for obesity.

BACKGROUND: Following gastric restrictive surgery, morbidly obese patients rarely achieve their ideal body weight defined by Metropolitan Life tables. The final body weight will depend on the initial body composition because there will be greater weight loss from fat than lean body mass. The purpose of this study was to develop a mathematical model that accurately estimates the rate and extent of weight loss following gastric bypass surgery. METHODS: Patients underwent gastric bypass followed by intensive medical therapy and serial bioelectrical impedance analysis (BIA) body composition measurements. Differential equations were derived to model weight loss. RESULTS: Weight loss in the fat and lean body compartments followed monoexponential decay kinetics with differing rate constants. Total body weight loss (W(T)) at time t was W(T) = k(f)(k(f) - k(l)) (W(f(o))e(-k(f)t) + W(l(o))e(-k(l)t)), where W(fo) and W(lo) are the initial fat and lean body masses determined by BIA and k(f) and k(l) are the rate constants for the fat and lean compartments, respectively. Following surgically induced weight loss, k(f) = 7.61 +/- 1.27 x 10(-2), and k(l) = -0.93 +/- 0.13 x 10(-2), with the ratio of residual sum of the squares to the total sum of the squares of 98.8%. CONCLUSION: Accurate prediction of weight loss depends on the initial fat and lean compartment mass since each of these loses weight at a different rate and to a different extent. When these effects are accounted for, the total body weight loss can be accurately predicted for any given time following surgery.

Alternative mRNA splicing in colon cancer causes loss of expression of neural cell adhesion molecule.

BACKGROUND: The neural cell adhesion molecule (NCAM) has numerous isoforms resulting from alternative splicing of mRNA. The 3 major isoforms found in adult tissue are (1) a 120-kDa protein that is linked to the plasma membrane by glycosylphosphatidylinositol; (2) a 140-kDa form that has a transmembrane component and a cytoplasmic tail with unknown function; and (3) a 180-kDa isoform that has an intracellular protein that binds the cytoskeleton. NCAM is capable of homotypic binding and therefore plays a role in cell-cell adhesion for cells expressing the 180-kDa isoform by anchoring groups of cells into epithelial sheets. NCAM-180 is the isoform found in colonocytes, and loss of expression is associated with clinically aggressive colon cancers. METHODS: Western blotting and reverse transcriptase-polymerase chain reaction were used to screen commercially available cell lines for NCAM-180 expression. For cell-line pairs with differential NCAM-180 expression, exon analysis was performed with reverse transcriptase-polymerase chain reaction to determine where the molecule was spliced, culminating in failed expression. These results were confirmed with exon analysis in colon cancers harvested at the time of laparotomy. RESULTS: Analysis of a SW480 cell line (derived from a patient's primary colon cancer lesion) revealed NCAM-180 expression, whereas no expression was found in the SW620 cell line (derived from a metastatic lesion from the same patient). Exon analysis of NCAM mRNA transcripts from SW620 revealed that the transcripts were truncated after exon 12. This region correlates to an area between 2 fibronectin-III domains on the NCAM protein. CONCLUSIONS: The most common site for NCAM alternative splicing is between the 2 fibronectin-III domains corresponding to the border between exons 12 and 13 of the NCAM gene. Loss of NCAM-180 expression in aggressive colon carcinoma results from a splice defect in the same area, which may result in defective intracellular adhesion between colonocytes.

Ultrasonographic evaluation of the cervix: transperineal versus endovaginal imaging.

OBJECTIVE: This study compares transperineal and endovaginal ultrasonography of the gravid cervix to evaluate image quality and assess for a systematic difference in cervical lengths measured by the 2 techniques. METHODS: Transperineal and endovaginal ultrasonography of the cervix was performed on 64 pregnant women. Two physicians reviewed the images and rated the relative diagnostic value of the techniques for assessing the cervix and for evaluating for placenta previa. Cervical length was measured prospectively in both techniques. Data were analyzed to determine if there is a systematic difference in length using the 2 approaches and if length differences are dependent on gestational age. RESULTS: There was a strong reviewer preference for endovaginal ultrasonographic images over transperineal images for both assessing the cervix (P< .001) and evaluating for placenta previa (P< .001). Despite this, transperineal and endovaginal ultrasonographic images were frequently rated as similar in diagnostic quality by both reviewers for depicting the cervix (35.9% of patients) and evaluating for placenta previa (57.8% of patients). The mean length of the cervix was slightly shorter at transperineal ultrasonography (28.4 mm) than at endovaginal ultrasonography (30.1 mm). When cervical lengths were subdivided by gestational age, however, a significant length discrepancy was found only in the 14- to 20-week gestational age range. In this age range, mean cervical length at transperineal ultrasonography (28.6 mm) averaged 5.5 mm less than at endovaginal ultrasonography (34.1 mm). CONCLUSIONS: Both transperineal and endovaginal ultrasonography can provide satisfactory images of the cervix, but endovaginal images are frequently superior to transperineal images. Endovaginal ultrasonography should be considered the optimal method for imaging the cervix in most situations. Transabdominal or transperineal ultrasonography can also be used, but if the cervix is not adequately depicted from these perspectives, endovaginal ultrasonography is indicated. Transperineal measurements of cervical length can be significantly shorter than endovaginal measurements, particularly before 20 weeks; therefore, short cervical lengths documented at transperineal ultrasonography before 20 weeks should be confirmed by endovaginal ultrasonography.

Human endomucin is an endothelial marker.

The identification of novel endothelial markers is important in the study of angiogenesis, and may have potential uses in cancer diagnosis and treatment. We have isolated potential markers of tumor angiogenesis by screening human umbilical vein endothelial cells (HUVECs) treated with tumor conditioned media. Using suppression subtractive hybridization (SSH), we found endomucin, a potential cell surface marker upregulated in this system. Human endomucin is predicted to encode a 261-aa, 27.5-kDa protein with a transmembrane sequence and multiple glycosylation sites. Northern and in situ hybridization studies show that human endomucin expression is largely, if not uniquely, endothelial cell-specific. Human endomucin is present abundantly in highly vascular tissues such as heart, kidney, and lung. It is seen in human aortic endothelial cells (HAECs) as well as in human microvascular endothelial cells (HMVECs). Furthermore, its expression is increased when endothelial cells are proliferating or are stimulated by tumor-conditioned media or specific angiogenic factors such as bFGF (basic fibroblast growth factor) and TNFalpha (tumor necrosis factor), suggesting that endomucin may have a role in tumor angiogenesis.

Peer review.

Peer review is essential for ensuring quality medical care. In the 1980s a physician-plaintiff prevailed in lawsuit filed against peer reviewers who excluded the physician from a hospital's medical staff. The peer reviewers had acted to preserve their own economic interests. A multimillion-dollar verdict against the peer reviewers destroyed the community's only multispecialty practice and received national attention. Congress reacted by passing the Health Care Quality Improvement Act that granted sweeping, legal immunity for peer reviewers but also created the National Practitioner's Data Bank. The combination of the establishment of a public repository for physicians malpractice and medical staff privileging activity in combination with the near complete legal protection of peer reviewers has converted peer review from an evaluative to a punitive process. The peer review process and the laws that govern it should be reformed to regain its ability to improve and assure quality without being a threat to physicians.

Human colon cancer cells deficient in DCC produce abnormal transcripts in progression of carcinogenesis.

Expressive loss of the tumor suppressor deleted in colon cancer (DCC) may be superior to lymph node status in predicting patient survival for intermediate stage colon cancer. A polymerase chain reaction (PCR)-based method for detecting DCC would be ideal as a prognostic indicator. DCC is an alternatively spliced molecule; thus, reliability of a PCR test for DCC will depend on amplifying only those regions of the molecule that are lost in the progression of colon cancer. For this reason, we studied a colon cancer cell line model at different stages of tumor progression to determine the alternative splice pattern for DCC. A commercially available colon cancer cell line system at different stages of tumor progression was used to identify which DCC exons are lost by western blot analysis, PCR, and RT-PCR techniques. Colon cancers express abnormal DCC transcripts. The proximal and distal exons are present (exons 2 and 28-29). Exons located in the center of the molecule are absent (6-7 and 18-23). This correlated to DCC protein loss in the cell lines. For clinical utility as a disease marker, exons in the middle portion of the DCC molecule that are spliced out should be utilized. Amplification of the proximal and distal regions will result in falsely concluding that DCC is present when its protein product is not expressed.