Novel association of thymic carcinoid with a germline mutation in a kindred with multiple endocrine neoplasia 1 (MEN1)

Multiple endocrine neoplasia 1 (MEN1) is an autosomal dominant syndrome characterized by a triad of endocrine (parathyroid, enteropancreatic and pituitary) tumors. Familial MEN1 is defined by one first-degree relative having at least one of these 3 main tumors, and is associated with germline mutations in the MEN1 gene on 11q13 in a large proportion of cases. MEN1 patients may also develop non-endocrine tumors, notably thymic carcinoid. These are rare tumors found predominantly in men, and are a major cause of death in MEN1 due to their insidious nature, lack of effective treatment and unpredictable recurrence. Prophylactic thymectomy has been advocated for prevention but continued surveillance for recurrence is necessary. Although genotype-phenotype correlation in MEN1-related thymic carcinoid is inconsistent, there is a high prevalence of truncating mutations in this condition. We describe a father and son with MEN1, associated with thymic carcinoid (father) and the truncating mutation R29X (son), which was not previously reported in MEN1-related thymic carcinoid, and review the literature about thymic carcinoids in MEN1. Our cases illustrate the importance of a high index of suspicion for early diagnosis and lifelong surveillance in MEN1, and the utility of genetic analysis in defining surveillance for MEN1-related thymic carcinoid.     

Clinical and economic burden of wound care in the tropics: a 5‐year institutional population health review

The aim of this study is to evaluate the clinical and economic burden of wound care in the Tropics via a 5‐year institutional population health review. Within our data analysis, wounds are broadly classified into neuro‐ischaemic ulcers (NIUs), venous leg ulcers (VLUs), pressure injuries (PIs), and surgical site infections (SSIs). Between 2013 and 2017, there were a total of 56 583 wound‐related inpatient admissions for 41 461 patients, with a 95.1% increase in wound episodes per 1000 inpatient admissions over this period (142 and 277 wound episodes per 1000 inpatient admissions in 2013 and 2017, respectively). In 2017, the average length of stay for each wound episode was 17.7 days, which was 2.4 times that of an average acute admission at our institution. The average gross charge per wound episode was USD $12 967. Among the 12 218 patients with 16 674 wound episodes in 2017, 71.5% were more than 65 years of age with an average Charlson Comorbidity Index (CCI) of 7.2. Half (51.9%) were moderately or severely frail, while 41.3% had two or more wound‐related admission episodes. In 2017, within our healthcare cluster, the gross healthcare costs for all inpatient wound episodes stand at USD $216 million within hospital care and USD $596 000 within primary care. Most NIU patients (97.2%) had diabetes and they had the most comorbidities (average CCI 8.4) and were the frailest group of patients (44.9% severely frail). The majority of the VLU disease burden was at the specialist outpatient setting, with the average 1‐year VLU recurrence rate at 52.5% and median time between healing and recurrence at 9.5 months. PI patients were the oldest (86.5% more than 65 years‐old), constituted the largest cohort of patients with 3874 patients at an incidence of 64.6 per 1000 admissions in 2017, and have a 1‐year all‐cause mortality rate of 14.3%. For SSI patients, there was a 125% increase of 14.2 SSI wound episodes per 1000 inpatient admissions in 2013 to 32.0 in 2017, and a 413% increase in wound‐related 30‐day re‐admissions, from 40 in 2013 (4.1% of all surgeries) to 205 (8.3% of all surgeries) in 2017. The estimated gross healthcare cost per patient ranges from USD $15789–17 761 across the wound categories. Similar to global data, there is a significant and rising trend in the clinical and economic burden of wound care in Tropics.     

Long-term Results of Comprehensive Clubfoot Release Versus the Ponseti Method: Which Is Better?

Background

Clubfoot can be treated nonoperatively, most commonly using a Ponseti approach, or surgically, most often with a comprehensive clubfoot release. Little is known about how these approaches compare with one another at longer term, or how patients treated with these approaches differ in terms of foot function, foot biomechanics, or quality-of-life from individuals who did not have clubfoot as a child.

Questions/purposes

We compared (1) focused physical and radiographic examinations, (2) gait analysis, and (3) quality-of-life measures at long-term followup between groups of adult patients with clubfoot treated either with the Ponseti method of nonsurgical management or a comprehensive surgical release through a Cincinnati incision, and compared these two groups with a control group without clubfoot.

Methods

This was a case control study of individuals treated for clubfoot at two separate institutions with different methods of treatment between 1983 to 1987. One hospital used only the Ponseti method and the other mainly used a comprehensive clubfoot release. There were 42 adults (24 treated surgically, 18 treated with Ponseti method) with isolated clubfoot along with 48 healthy control subjects who agreed to participate in a detailed analysis of physical function, foot biomechanics, and quality-of-life metrics.

Results

Both treatment groups had diminished strength and motion compared with the control subjects on physical examination measures; however, the Ponseti group had significantly greater ankle plantar flexion ROM (p < 0.001), greater ankle plantar flexor (p = 0.031) and evertor (p = 0.012) strength, and a decreased incidence of osteoarthritis in the ankle and foot compared with the surgical group. During gait the surgical group had reduced peak ankle plantar flexion (p = 0.002), and reduced sagittal plane hindfoot (p = 0.009) and forefoot (p = 0.008) ROM during the preswing phase compared with the Ponseti group. The surgical group had the lowest overall ankle power generation during push off compared with the control subjects (p = 0.002). Outcome tools revealed elevated pain levels in the surgical group compared with the Ponseti group (p = 0.008) and lower scores for physical function and quality-of-life for both clubfoot groups compared with age-range matched control subjects (p = 0.01).

Conclusions

Although individuals in each treatment group experienced pain, weakness, and reduced ROM, they were highly functional into early adulthood. As adults the Ponseti group fared better than the surgically treated group because of advantages including increased ROM observed at the physical examination and during gait, greater strength, and less arthritis. This study supports efforts to correct clubfoot with Ponseti casting and minimizing surgery to the joints, and highlights the need to improve methods that promote ROM and strength which are important for adult function.

Level of Evidence

Level III, prognostic study.     

Temperature rhythms in native Alaskan and Caucasian children

The oral temperatures of native Eskimo and Caucasian school children between 10 and 13 years of age were measured at four times of day and once at night on four consecutive days during the Spring and Fall. There were significant differences across the daily measures indicating circadian entrainment. There were no differences between the native and Caucasian groups indicating that earlier reports of less well defined circadian rhythms in adult native Eskimos were not due to inherent rhythm limitations in native Eskimos.     

Curcumin-Rich Curry Consumption and Neurocognitive Function from 4.5-Year Follow-Up of Community-Dwelling Older Adults (Singapore Longitudinal Ageing Study)

The potential neurocognition protective effects of dietary curcumin in curry consumed with food was investigated in this study of 2734 community-dwelling adults (aged ≥ 55, mean ± SD: 65.9 ± 7.4). We analyzed longitudinal data of baseline curry consumption (“never or rarely”, “occasionally”: <once a month, “often”: >once a month and <once a week, “very often”: >once a week or daily) and baseline and 4.5-year follow-up cognitive function in mixed model analyses controlling for confounding risk factors. Significant between-exposure differences were found for Digit Span-Backward (DS-B), Verbal Fluency-Animals (VF-A) and Block Design (BD). Compared to “never or rarely” consumption, “very often” and “often” consumptions were associated with higher DS-B performance; “very often”—with higher VF-A, and “occasional”, “often” and “very often” consumptions—with higher BD: Cohen’s d: from 0.130 to 0.186. Among participants with cardiometabolic and cardiac diseases (CMVD), curry consumption was associated with significantly higher DS-B and VF-A. Among CMVD-free participants, curry consumption was associated with significantly higher DS-B, VF-A and BD: Cohen’s d: from 0.098 to 0.305. The consumption of dietary curcumin was associated with the maintenance over time of higher functioning on attention, short-term working memory, visual spatial constructional ability, language and executive function among community-dwelling older Asian adults.