The impact of bowel dysfunction on health-related quality of life after rectal cancer surgery: a systematic review.

BACKGROUND: Symptoms of bowel dysfunction after sphincter-preserving rectal cancer surgery have an important impact on health-related quality of life (HRQOL), but that relationship is complex. A better understanding of this relationship allows for better informed shared decision-making about surgery. Our objective was to perform a systematic review to determine which HRQOL domains are most affected by postoperative bowel dysfunction. METHODS: A systematic review of the CINAHL, Cochrane Library, Embase, Medline, PsycInfo, PubMed, Web of Science, and Scopus databases was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included studies that evaluated bowel function after sphincter-preserving rectal cancer surgery and assessed HRQOL using a validated instrument. The quality of HRQOL analysis was assessed using an 11-item checklist. The main outcome was the impact bowel dysfunction had on global and domain specific quality-of-life indices. The impact was evaluated for clinical relevance using the Minimum Clinical Important Difference (MCID) for each specific HRQOL instrument. RESULTS: Out of 952 unique citations, 103 studies were full-text reviews. Eighteen studies met the inclusion criteria (4 prospective cohorts and 9 cross-sectional studies). Of the 15 studies with long-term follow-up, the time to assessment after surgery ranged from 1.2 to 14.6 years. The low anterior resection syndrome score and European Organization for Research and Treatment core quality-of-life questionnaire (EORTC QLQ-C30) were the most commonly used instruments. Medium and large magnitudes in MCID were seen for global health, social functioning, emotional functioning, fatigue, diarrhea, and financial difficulties. Among included studies, the most consistently reported functional domains affected by bowel function were social functioning and emotional functioning. CONCLUSIONS: Following sphincter-preserving rectal cancer surgery, poor bowel function mainly affects the social and emotional functional domains of HRQOL, which in turn impact global scores. This finding can help inform patients about expected changes in HRQOL after rectal cancer surgery and facilitate individualized treatment decisions.

Trajectory of change of low anterior resection syndrome over time after restorative proctectomy for rectal adenocarcinoma.

BACKGROUND: Restorative proctectomy for rectal cancer is associated with a high incidence of low anterior resection syndrome (LARS), but few studies report longitudinal results for bowel function. The aim of our study was to examine the trajectory of change of LARS over the first 18 months after restorative proctectomy for rectal cancer. METHODS: A prospective database measuring functional outcomes in rectal cancer patients from a single university-affiliated specialist colorectal referral center from 10/2018 to 03/2020 was queried. Patients were included in this study if they underwent restorative proctectomy for rectal cancer and had at least three assessments in the first 18 months after primary surgery or after closure of proximal diversion. Bowel function was assessed using the LARS score, administered at every surveillance follow-up after restoration of bowel continuity. Latent-class growth curve (trajectory) analysis was used to identify different trajectories of LARS changes over the first 18 months and group patients into these trajectory groups. These groups were then compared to identify predictors for each trajectory. RESULTS: A total of 95 patients were included (63 males, mean age. 61.3 ± 12.5 years). Trajectory analysis identified three distinct trajectory groups. Group 1 had stable minimal LARS over time (26%). Group 2 had early LARS scores consistent with the minor LARS category and improved with time (28%). Group 3 had persistently high LARS scores (45%). Neoadjuvant therapy, intersphincteric resection, and proximal diversion were more common in group 3. CONCLUSIONS: We identified three main trajectories of change of LARS in the 18 months after restorative proctectomy. These data may be used to better inform patients of their expected postoperative bowel function.

Two nasal swabs may not be enough to exclude SARS-CoV-2 infection in symptomatic patients.

Abstracts: The spread of COVID-19 (COronaVIrus Disease 2019), due to SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) has taken on dramatic pandemic proportions, affecting over 100 countries in a matter of weeks. Italy has had 237,828 confirmed cases according to the Istituto Superiore di Sanità as of May 13, and 34,448 deaths (1).

Caffeine prevents prostaglandin E1-induced disturbances in respiratory control in neonatal rats: implications for infants with critical congenital heart disease.

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.

Cardiorespiratory events in preterm infants: etiology and monitoring technologies.

Every year, an estimated 15 million infants are born prematurely (<37 weeks gestation) with premature birth rates ranging from 5 to 18% across 184 countries. Although there are a multitude of reasons for this high rate of preterm birth, once birth occurs, a major challenge of infant care includes the stabilization of respiration and oxygenation. Clinical care of this vulnerable infant population continues to improve, yet there are major areas that have yet to be resolved including the identification of optimal respiratory support modalities and oxygen saturation targets, and reduction of associated short- and long-term morbidities. As intermittent hypoxemia is a consequence of immature respiratory control and resultant apnea superimposed upon an immature lung, improvements in clinical care must include a thorough knowledge of premature lung development and pathophysiology that is unique to premature birth. In Part 1 of a two-part review, we summarize early lung development and diagnostic methods for cardiorespiratory monitoring.

Cardiorespiratory events in preterm infants: interventions and consequences.

Stabilization of respiration and oxygenation continues to be one of the main challenges in clinical care of the neonate. Despite aggressive respiratory support including mechanical ventilation, continuous positive airway pressure, oxygen and caffeine therapy to reduce apnea and accompanying intermittent hypoxemia, the incidence of intermittent hypoxemia events continues to increase during the first few months of life. Even with improvements in clinical care, standards for oxygen saturation targeting and modes of respiratory support have yet to be identified in this vulnerable infant cohort. In addition, we are only beginning to explore the association between the incidence and pattern of cardiorespiratory events during early postnatal life and both short- and long-term morbidity including retinopathy of prematurity, growth, sleep-disordered breathing and neurodevelopmental impairment. Part 1 of this review included a summary of lung development and diagnostic methods of cardiorespiratory monitoring. In Part 2 we focus on clinical interventions and the short- and long-term consequences of cardiorespiratory events in preterm infants.

Hypoxia-hyperoxia paradigms in the development of oxygen-induced retinopathy in a rat pup model.

BACKGROUND: Retinopathy of prematurity [ROP] continues to be a significant clinical problem in preterm infants. There is a need for animal models to better understand the roles of hypoxia/hyperoxia in the pathogenesis and management of ROP. OBJECTIVES: To test the hypothesis that multiple daily cycles of intermittent hypoxia, followed by brief hyperoxia, would provide a clinically relevant protocol for generation of ROP in a rat pup. METHODS: Rat pups were exposed for the first 14 days to one of three protocols: room air [RA], sustained cycles of hyperoxia/hypoxia [SHH] as previously employed to produce ROP in rat pups, and intermittent hypoxia/hyperoxia [IHH] in order to more closely simulate clinical conditions in preterm infants. Retinae were obtained at 18 days and imaged for both avascularization and neovascularization. RESULTS: As expected, the SHH group demonstrated significantly increased avascularity [40.9 ± 7.9% of retina] which was minimal in both RA and IHH groups. All SHH exposed pups exhibited neovascularization which occurred in 5/7 IHH exposed retinae versus 0 in the RA group [p = 0.02]. However, mean number of clock hours of neovascularization after IHH was 1.9 ± 2.1 which did not differ from the RA group, and was less than in the SHH group [8.3 ± 1.9, p < 0.001]. CONCLUSION: A more clinically relevant intermittent hypoxia/hyperoxia [IHH] protocol does not produce the same degree of ROP as the traditional sustained hypoxia/hyperoxia [SHH] paradigm. Nonetheless, further refinement of our model may provide a suitable model for understanding the lesser degrees of ROP which predominate in preterm infants.

The effect of red blood cell transfusion on intermittent hypoxemia in ELBW infants.

OBJECTIVE: To test the hypothesis that the effect of red blood cell (RBC) transfusion on intermittent hypoxemia (IH) in extremely low birth weight (ELBW) infants is dependent on postnatal age. STUDY DESIGN: Oxygen saturation of 130 ELBW infants, who required transfusion, was monitored continuously for the first 8 weeks of life. We compared the characteristics of IH (SpO2⩽80% for ⩾4 s and ⩽3 min), 24 h before and both 24 h and 24 to 48 h after each RBC transfusion at three distinct time periods: Epoch 1, 1 to 7 days; Epoch 2, 8 to 28 days; and Epoch 3, >28 days. RESULT: In Epoch 1, the frequency and severity of IH events were not significantly different before and after transfusion. In both Epochs 2 and 3 there was a decrease in IH frequency and severity 24 h after RBC transfusion that persisted for 48 h. In addition, there was a decrease in the overall time spent with SpO2 ⩽80% which persisted for 24 h after transfusion in Epochs 1 and 3, and for 48 h in Epoch 3. CONCLUSION: The benefit of RBC transfusion on IH is age dependent as improvement in the frequency and severity of IH after transfusion only occurs beyond the first week of life. These observations will aid clinician's decision making by clarifying the benefit of RBC transfusions on patterns of oxygenation in preterm infants.

Vulnerability of neonatal respiratory neural control to sustained hypoxia during a uniquely sensitive window of development.

The first postnatal weeks represent a period of development in the rat during which the respiratory neural control system may be vulnerable to aberrant environmental stressors. In the present study, we investigated whether sustained hypoxia (SH; 11% O2) exposure starting at different postnatal ages differentially modifies the acute hypoxic (HVR) and hypercapnic ventilatory response (HCVR). Three different groups of rat pups were exposed to 5 days of SH, starting at either postnatal age 1 (SH1-5), 11 (SH11-15), or 21 (SH21-25) days. Whole body plethysmography was used to assess the HVR and HCVR the day after SH exposure ended. The primary results indicated that 1) the HVR and HCVR of SH11-15 rats were absent or attenuated (respectively) compared with age-matched rats raised in normoxia; 2) there was a profoundly high (∼84% of pups) incidence of unexplained mortality in the SH11-15 rats; and 3) these phenomena were unique to the SH11-15 group with no comparable effect of the SH exposure on the HVR, HCVR, or mortality in the younger (SH1-5) or older (SH21-25) rats. These results share several commonalities with the risk factors thought to underlie the etiology of sudden infant death syndrome, including 1) a vulnerable neonate; 2) a critical period of development; and 3) an environmental stressor.

Impaired hypoxic ventilatory response following neonatal sustained and subsequent chronic intermittent hypoxia in rats.

Neonatal chronic intermittent hypoxia (CIH) enhances the ventilatory sensitivity to acute hypoxia (acute hypoxic ventilatory response, HVR), whereas sustained hypoxia (SH) can have the opposite effect. Therefore, we investigated whether neonatal rats pre-treated with SH prior to CIH exhibit a modified HVR. Rat pups were exposed to CIH (5% O2/5min, 8h/day) between 6 and 15 days of postnatal age (P6-15) after pre-treatment with either normoxia or SH (11% O2; P1-5). Using whole-body plethysmography, the acute (5min, 10% O2) HVR at P16 (1 day post-CIH) was unchanged following CIH (67.9±6.7% above baseline) and also SH (58.8±10.5%) compared to age-matched normoxic rats (54.7±6.3%). In contrast, the HVR was attenuated (16.5±6.0%) in CIH exposed rats pre-treated with SH. These data suggest that while neonatal SH and CIH alone have little effect on the magnitude of the acute HVR, their combined effects impose a synergistic disturbance to postnatal development of the HVR. These data could provide important insight into the consequences of not maintaining adequate levels of oxygen saturation during the early neonatal period, especially in vulnerable preterm infants susceptible to frequent bouts of hypoxemic events (CIH) that are commonly associated with apnea of prematurity.

Physiologic basis for intermittent hypoxic episodes in preterm infants.

Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are commonly underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia [IH] progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks six to eight. Over this period of unstable respiratory control, increased oxygen-sensitive peripheral chemoreceptor activity has been associated with a higher incidence of apnea of prematurity. In contrast, infants with bronchopulmonary dysplasia [chronic neonatal lung disease] exhibit decreased peripheral chemosensitivity, although the effect on respiratory stability in this population is unclear. Such episodic hypoxia/reoxygenation in early life has the potential to sustain a proinflammatory cascade with resultant multisystem, including respiratory, morbidity. Therapeutic approaches for intermittent hypoxic episodes comprise careful titration of baseline or supplemental inspired oxygen as well as xanthine therapy to prevent apnea of prematurity. Characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management.

Effect of postnatal intermittent hypoxia on growth and cardiovascular regulation of rat pups.

BACKGROUND: Intermittent hypoxic episodes are common among preterm infants, although longer term consequences on growth pattern and cardiovascular regulation are unclear. Furthermore, the effects of intermittent hypoxia (IH) may depend on the pattern of hypoxia-reoxygenation. OBJECTIVES: We tested the hypothesis that a clustered versus dispersed pattern of repetitive IH during early postnatal life would induce differential long-term alteration in growth and cardiovascular regulation. METHODS: Sprague-Dawley rat pups were exposed to room air or to one of two patterns of IH (clustered vs. dispersed) from 1 to 7 days of life. Body weight was measured daily for the first 8 days and weekly from weeks 2 to 8. Blood pressure (BP) and heart rate were measured weekly from weeks 4 to 8 using a noninvasive tail-cuff method for awake, nonanesthetized animals. RESULTS: Exposure to both patterns of repetitive IH induced early growth restriction followed by later catch-up of growth to controls 3 weeks after completion of IH exposures. IH-exposed rats exhibited a sustained decrease in heart rate regardless of the hypoxic exposure paradigm employed. In contrast, a differential response was seen for arterial pressure; the clustered paradigm was associated with a significantly lower BP versus controls, while the pups exposed to the dispersed paradigm showed no effect on BP. CONCLUSION: We speculate that repetitive IH during a critical developmental window and regardless of IH exposure paradigm contributes to prolonged changes in sympathovagal balance of cardiovascular regulation.

Hospital discharge criteria following colorectal surgery: a systematic review.

AIM: The aim of this study was to identify and synthesize the hospital discharge criteria that have been used in the colorectal surgery literature. METHODS: A systematic literature search was conducted using eight bibliographic databases. Searches were limited to English language journal articles published between January 1996 and October 2009. Primary research applying hospital discharge criteria following colorectal surgery was included. Study selection was made independently by two reviewers. Discharge criteria were extracted from each included study. RESULTS: The 156 studies identified by the search strategy described 70 different sets of criteria to indicate readiness for discharge. The majority of studies applied a combination of three or four criteria; those most frequently cited were tolerance of oral intake (80%), return of bowel function (70%), adequate pain control (44%) and adequate mobility (35%). End-points employed to determine the achievement of criteria were generally poorly defined. CONCLUSION: A variety of hospital discharge criteria were applied in the colorectal surgery literature. Development of standardized criteria will allow more accurate comparison of results between studies assessing hospital length of stay or other discharge-related outcome measures.

Implementation and analysis of a pilot in-hospital newborn screening program for glucose-6-phosphate dehydrogenase deficiency in the United States.

OBJECTIVE: The purpose of this study was to analyze a targeted screening program for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDdef) and clinical outcomes of G6PD-deficient vs G6PD normal newborns. STUDY DESIGN: Retrospective chart review for 1578 male newborns was performed. The study group was those screened for G6PDdef. Comparisons between G6PD-deficient and normal infants were made with χ (2)-test and unpaired t-test. RESULT: A total of 1095 male newborns were screened, 11.1% had G6PDdef. 97.8% of screen results were reported by 48 h. Total bilirubin (TB) levels in deficient infants were significantly higher than in normal infants throughout birth hospitalization and they were more likely to receive phototherapy. Nineteen screened newborns were rehospitalized for hyperbilirubinemia, 47% had G6PDdef. CONCLUSION: In-hospital newborn screening for G6PDdef with rapid turnaround time is possible. G6PDdef is a risk factor for hyperbilirubinemia in American newborns. US centers with large at-risk populations can identify newborns at risk for severe hyperbilirubinemia with similar screening.

Surgical approach does not affect perioperative respiratory morbidity in living donor nephrectomy: comparison between anterior subcostal incision and flank incision.

BACKGROUND: Living donor nephrectomy has been a routine surgical procedure that significantly increased the number of organs for patients with end-stage renal disease. Upper abdominal surgeries, especially when performed with an open approach, usually lead to a postoperative reduction in lung volumes and pulmonary compliance, which may predispose to the development of atelectasis and pulmonary mucus retention, important risk factors for postoperative pulmonary infections. AIM: This study sought to compare lung function impairment, pain, and the incidence of postoperative pulmonary complications among live nephrectomy donors undergoing either an open donor nephrectomy through an anterior subcostal incision (SC) or a flank incision (FL). PATIENTS AND METHODS: Between 2006 and 2008, 110 subjects (44 SC/66 FL) had their pulmonary functions (spirometry) and pain (visual analog scale) evaluated preoperatively as well as on postoperative days 1, 2, 3, and 5. Postoperative pulmonary complications were evaluated daily by a pulmonary physician. A chest radiograph was obtained on postoperative day 2 to evaluate the presence of atelectasis. RESULTS: Both groups were similar before surgery. Patients in both groups showed decreased pulmonary function from day 1 to 3 (P < .05). Subjective pain was increased until day 5 (P < .05) with a higher incidence of atelectasis among 36% FL vs. 25% SC. (P > .05). CONCLUSION: Living donor nephrectomy through either a flank incision or an anterior subcostal incision showed similar degrees of postoperative pain, decreased lung function, and pulmonary complications.

Characterization of cardiorespiratory events following gastroesophageal reflux in preterm infants.

OBJECTIVE: The aim of this study was to characterize cardiorespiratory events in preterm infants after both acid and nonacid gastroesophageal reflux (GER) as detected by pH and multiple intraluminal impedance (MII). STUDY DESIGN: Twelve hour overnight studies were performed in 71 preterm infants (gestational age 29.4±3.0 weeks, birth weight 1319±496 g). Apnea ≥10 s in duration, bradycardia ≤80 b.p.m. and oxygen desaturation ≤85% that occurred within 30 s after the initiation of GER were classified as associated with GER. RESULT: A total of 12,957 cardiorespiratory events and 4164 GER episodes were documented. Less than 3% of all cardiorespiratory events were preceded by GER constituting 3.4% of apnea, 2.8% of oxygen desaturation and 2.9% of bradycardia events. GER did not prolong cardiorespiratory event duration or increase severity. In contrast, GER was associated with a shorter duration of oxygen desaturation events (7.8±4.6 vs 6.3±5.6 s, P<0.05). CONCLUSION: GER is rarely associated with cardiorespiratory events, and has no detrimental effect on cardiorespiratory event duration or severity.

Apnea, bradycardia and desaturation in preterm infants before and after feeding.

OBJECTIVE: A common clinical impression is that both gastroesophageal reflux (GER) and cardiorespiratory events increase after feeding in preterm infants. We aimed to measure objectively the effects of feeding on GER, apnea, bradycardia and desaturations. STUDY DESIGN: We conducted a retrospective review of premature infants with a gestational age of 23 to 37 weeks at birth and a post-conceptional age of 34 to 48 weeks, who were referred for multichannel intraluminal impedance (MII), pH probe and 12-h apnea evaluation. Cardiorespiratory and GER event rates during pre- and post-feeding intervals were compared. RESULT: Thirty-six infants met the inclusion criteria. More GER events occurred after a feed than before (P=0.012). After feeds, reflux was less acidic and higher in the esophagus (P<0.05). In contrast, the rates of apnea, bradycardia and desaturations were not altered by infant feeding. Apnea of >5 s occurred at a median frequency of 0 (range 0 to 3) events per hour before a feed and 0 (0 to 2) events per hour after a feed (P=0.61). CONCLUSION: The frequency, height and pH of GER are significantly altered by feedings in preterm infants. However, the common clinical impression that apnea, bradycardia and desaturations are more prevalent after feeding is not supported.

Locoregionally advanced nasopharyngeal carcinoma: induction chemotherapy with cisplatin and 5-fluorouracil followed by radiotherapy and concurrent cisplatin: a phase II study.

BACKGROUND: Chemoradiotherapy is the current standard of care for locoregionally advanced nasopharyngeal carcinoma. The purpose of this study was to assess the feasibility and efficacy of induction chemotherapy (CHT) followed by concomitant chemoradiotherapy in this patient population. PATIENTS AND METHODS: In this single-arm, phase II study, patients with locoregionally advanced nasopharyngeal carcinoma were treated with 3 cycles of induction CHT with cisplatin (100 mg/m(2) on day 1) and 5-fluorouracil (1,000 mg/m(2) continuous infusion on days 1-4) followed by 3 cycles of cisplatin (100 mg/m(2) on days 1, 22 and 43) and concurrent radiotherapy up to 70 Gy. The primary endpoint was objective response. RESULTS: Thirty-four patients were enrolled, and all completed both induction treatment and subsequent chemoradiotherapy. Objective response rates were 79.4% (95% CI 62.1-91.3) and 85.3% (95% CI 68.9-95.0) after induction CHT and chemoradiation, respectively. Treatment was well tolerated and toxicity was manageable. At a median follow-up of 29 months, 3-year overall survival and progression-free survival rates are 80.0% (95% CI 0.64-0.95) and 54.0% (95% CI 0.36-0.73), respectively. CONCLUSIONS: Induction CHT with cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy is a feasible and active regimen for patients with stage IIB-IVB nasopharyngeal carcinoma. This regimen resulted in excellent locoregional disease control and overall survival.

The effect of inhaled nitric oxide on pulmonary function in preterm infants.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) in preterm infants is associated with impaired alveolar growth, inflammation and airway hyperreactivity. In animal models of BPD, inhaled nitric oxide (NO) improves alveolar growth and inhibits airway smooth muscle proliferation. This study was designed to assess the effect of inhaled NO on resistance and compliance in ventilated preterm infants with evolving BPD. STUDY DESIGN: Expiratory resistance and compliance of the respiratory system were measured in 71 ventilated preterm infants, < or = 32 weeks gestation, randomized to NO (n=34) versus placebo (n=37) for > or = 24 days at 7 to 21 days of life. RESULT: At baseline expiratory resistance (231+/-71 versus 215+/-76 cm H(2)O l(-1) s(-1)) and compliance (0.49+/-0.14 versus 0.53+/-0.13 ml cm H(2)O(-1) kg(-1)) were comparable between placebo and NO groups, respectively. There was no effect of NO on expiratory resistance or compliance at 1 h, 1 week or 2 weeks of study gas administration. CONCLUSION: NO had no short- or medium-term effect on expiratory resistance or compliance in ventilated preterm infants.